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ImmunoVision – issue 6 of our new newsletter

December’s ImmunoVision brings you a special end of year offer – a 20% discount on books. Further-more, immunology content published in the Encyclopaedia of Life Sciences and the Cochrane Library are highlighted, as are reviews series on NK cells and the translational mini-review series on B cell- directed therapies. Read on for details of these and other Wiley-Blackwell immunology-related content.

URL: www3.interscience.wiley.com/journal/25061/home/news/index.htmle-mail: immunovisions@wiley.com

ImmunoFeature

Coming soon to Immunological Reviews! VOLUME 233: Inflammatory Arthritis

Guest Editor: Terri Laufer

Inflammatory arthritis is the pathologic consequence of disease states as varied as chronic autoimmune diseases like rheumatoid arthritis and ankylosing spondylitis, autoinflammatory crystal-induced diseases like gout, and infectious arthritis. This issue of Immunolo-gical Reviews focuses on the pathophysiology of auto-immune and crystal- induced arthritis.

This volume highlights ongoing research addressing the causes and consequences of chronic inflammatory arthritis. Topics range from the genetics of systemic rheumatic diseases, the inappropriate regulation of the immune response and the end-organ processes of synoviocyte proliferation and the disruption of bone homeostasis.

Articles include:

The role of antibodies in inflammatory arthritisBob Eisenberg

Fibroblast-like synoviocytes: Key effector cells in rheumatoid arthritisGary Firestein

Immunologic mechanisms of lyme arthritisBridgitte Huber

And many more…

For further information about Immunological Reviews and to subscribe visit: www.immunologicalreviews.com

ImmunoDigest

Visualizing Protein Activity in a Flow

The functional status of a protein often depends upon interactions with other proteins and on post-translational modifications (e.g. phos-phorylation). An obstacle for detection of protein phosphorylation with immunofluorescence is cross-reactivity of the antibodies with other proteins. In situ proximity ligation assays (PLA) depend on recognition of target molecules by two antibodies to yield a signal via localized rolling circle amplification. This offers a valuable opportunity to ensure that the right protein is detected, and that its interaction partners or its phosphorylation status are recorded using two different antibodies. Leuchowius and coworkers used in situ PLA in combination with flow cytometry for detection of EGFR homo- and heterodimers as well as EGFR-phosphorylation. Dimerization of EGFR and HER2 was not af-fected by EGF-stimulation, suggesting that the proteins exist as dimers prior to stimulation. For detection of EGFR phosphorylation, in situ PLA was found clearly superior to immunofluorescence with regard to selectivity and signal strength.

Leuchowius, K.-J. et al., Cytometry A 2009 75: 833-839.http://doi.wiley.com/10.1002/cyto.a.20771

December2009

ImmunoVision

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ImmunoProtocols

Current Protocols: The Fine Art of Experimentation

Discover the new Current Protocols website, currentprotocols.com, where you can

• browse, rate, and comment on, our entire collection of protocols• sign up for New Protocol Alerts• access an excellent selection of free-to-use Tools and Calculators• post or answer questions in our forums• view helpful video protocols• read and comment on our blog, Beyond the Bench• register and upload your own protocols to share with the Current Protocols community

What’s new in Current Protocols in Immunology

Visualization of Multiprotein Complexes by Flow CytometryMultiprotein complexes and other protein-protein interactions play important roles in virtually all cellular processes. Analysis of coimmu-noprecipitation of protein complexes by flow cytometry (IP-FCM, or “the fly-p” method) provides a sensitive means to measure these inter-actions in the native/nondenatured state. First, immunoprecipitating antibodies are covalently coupled to polystyrene latex beads whose low autofluorescence is compatible with flow cytometry. These antibody-coupled beads are used to immunoprecipitate a specific protein (primary analyte) present in cell lysates. Finally, the protein complexes associated with the beads are probed with fluorochrome-conjugated antibodies specific for interaction partners, or secondary analytes, that may be associated with the primary analyte. The use of quantitative flow cytometric methodology can allow the semiquantitative fluore-scence data generated to be converted into estimated numbers of coassociated molecules on the beads. The method represents a robust technique to assess native protein-protein interactions without requiring genetic engineering or large sample sizes.Curr. Protoc. Immunol. 87:5.9.1-5.9.14. http://doi.wiley.com/10.1002/0471142735.im0509s87

TRAF-Mediated TNFR-Family SignalingThe tumor necrosis factor (TNF) superfamily consists of a wide variety of cell-bound and secreted proteins that regulate numerous cellular processes. In particular, TNF-family proteins regulate the proliferati-on and death of tumor cells, as well as activated immune cells. This overview discusses the mammalian TNF receptor-associated factors (TRAFs), of which TRAF1, 2, 3, 5, and 6 have been shown to interact directly or indirectly with members of the TNF receptor superfamily. Structural features of TRAF proteins are described along with a discussion of TRAF-interacting proteins and the signaling pathways activated by the TRAF proteins. Finally, we examine the phenotypes observed in TRAF-knockout mice.Curr. Protoc. Immunol. 87:11.9D.1-11.9D.19.http://doi.wiley.com/10.1002/0471142735.im1109ds87

A cell on the go-go: Eosinophil-o

Eosinophils have been described as ‘‘pleiotropic multifunctional’’ cells that have their tendrils in a wide variety of immunoregulatory and inflammatory ‘‘pots’’. And when they don’t work, all sorts of things can go wrong – asthma, allergy, and parasite infections for a start. As they mature, eosino-phils are posted to various tissues – mammary gland, thymus, lung, uterus, and gastrointestinal tract are a few. At inflammatory sites, they may be pro- or anti-inflamm-atory depending on the balance of control exerted through cytokines, chemokines, growth factors and more. Using 2DE MALDI-TOF and TOF/TOF, Straub et al., identified 3141 expressed proteins. Bronchi-al asthma is a particularly serious case in point – 16 million adults and 6 million children developed the eosinophil-linked disease in 2006, but even with all of the – kine and other control points, no curative or prognostic biomarkers have been found to date. Clearly, a target for further discovery work.Straub, C. et al., Proteomics Clin. Appl. 2009. 3: 1151–1173.http://doi.wiley.com/10.1002/prca.200900043

Catalytic antibodies: balancing between Dr. Jekyll and Mr. Hyde

Catalytic antibodies, or “ab-zymes”, are immunoglobulin molecules with enzymatic func-tions. Abzymes occur naturally, displaying an inverse relation-ship of high specificity with low catalytic function, and have been shown to have beneficial effects in some pathological processes but deleterious effects in others. The obvious therapeutic advantage of the specificity afforded by anti-body coupled enzymatic activity has prompted great interest in the artificial design of abzymes. Further, dramatic breakthroughs in antibody engineering and expression technologies have enabled a promising source of high precision “catalytic vaccines’ which may offer significant ad-vantages over current therapeutic options. Still, the conflicting Dr. Jekyll and Mr. Hyde-protective and destructive -natures of catalytic antibodies need to be considered carefully before they are used as therapeutic agents. Gabibov et al. BioEssays 2009. 31: 1161 – 1171.http://doi.wiley.com/10.1002/bies.200900020

BioDigest

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ImmunoFeature

Autophagy in Nonmammalian Systems (Keynote)Jahda H Hill, Eric H Baehreckehttp://doi.wiley.com/10.1002/9780470015902.a0021582 HIV Vaccine Approaches (Keynote)A McKnight, Daniel J Penningtonhttp://doi.wiley.com/10.1002/9780470015902.a0021550

Paraneoplastic Neurologic Syn-dromes (Keynote)Peter Maat, Peter AE Sillevis Smitthttp://doi.wiley.com/10.1002/9780470015902.a0021410 Caspases in Inflammation and Immunity (Keynote)Philippe M LeBlanc, Maya Salehhttp://doi.wiley.com/10.1002/9780470015902.a0021990

Multiple Sclerosis (Introductory)Jana Preiningerova, Roberto Bom-prezzi, Timothy L Vollmer, Stephen G Waxmanhttp://doi.wiley.com/10.1002/9780470015902.a0000192.pub2

Epitopes (Keynote)Claude P Muller, Monique Jacobyhttp://doi.wiley.com/10.1002/9780470015902.a0000514.pub2

Antigens: Thymus-dependent (Keynote)Martin F Bachmannhttp://doi.wiley.com/10.1002/9780470015902.a0000502.pub2

Lymphatic System (Introductory)Wayne G Kimpton, Elizabeth A Washingtonhttp://doi.wiley.com/10.1002/9780470015902.a0000523.pub2

Immunological Tolerance: Therapeutic Induction (Keynote)Stephen M Andertonhttp://doi.wiley.com/ 10.1002/9780470015902.a0001285.pub2

Hypersensitivity: Immunological (Introducotry)Wayne R Thomas, Paula T Cun-ninghamhttp://doi.wiley.com/10.1002/9780470015902.a0000964.pub2

Molecular Mimicry (Keynote)Madeleine White Cunninghamhttp://doi.wiley.com/10.1002/9780470015902.a0000958.pub2

Natural Antibodies (Keynote)Moncef Zoualihttp://doi.wiley.com/10.1002/9780470015902.a0001213.pub2

Immunoelectrophoresis (Keynote)Stanley S Levinsonhttp://doi.wiley.com/10.1002/9780470015902.a0001136.pub2

Follicular Dendritic Cells (B Lymphocyte Stimulating) (Introductory)Mohey Eldin M El Shikh, Rania M El Sayed, John G Tew, Gregory F Burtonhttp://doi.wiley.com/10.1002/9780470015902.a0001129.pub2

Cytokines (Introductory)Heather M Wilson, Robert N Barkerhttp://doi.wiley.com/10.1002/9780470015902.a0000929.pub2

Immune Complex Disease (Keynote)Kenneth J Hardy, Amrit P Singh, Richard D de Shazohttp://doi.wiley.com/10.1002/9780470015902.a0002164.pub2

Inbred Animal Strains (Keynote)Tsutomu Kurosawahttp://doi.wiley.com/10.1002/9780470015902.a0001442.pub2

Articles within the Encyclopedia of Life Sciences (ELS) are aimed at researchers, students and teachers alike. Since all articles have been commissioned and peer-reviewed, a balanced representation of the literature is ensured.

The articles within ELS are written by leaders in the field to provide comprehensive and authoritative coverage of this subject area and Articles are divided into three different categories. Introductory articles have been written primarily for undergraduate and non-specialists requiring the basic concepts of a particular subject. Advanced articles provide a more detailed discussion of specialist subjects, equivalent to that found in graduate level texts. Keynote articles provide a platform for debate where controversial issues and “hot topics” can be discussed.

See the latest articles published in ELS in the field of immunology:

Immunofluorescence: Dyes and Other Haptens Conjugated with Antibodies (Keynote)Wolfgang Härtig, Jean-Marc Fritschyhttp://doi.wiley.com/10.1002/9780470015902.a0002626.pub2

AIDS: Clinical Manifestations (Keynote)Christoph Boesecke, Gregory J Dore, David A Cooperhttp://doi.wiley.com/10.1002/9780470015902.a0002237.pub2

Signal Transduction Pathways in Development and Immunity: NFκB/Rel Pathways (Keynote)Thomas D Gilmore, Y Tony Iphttp://doi.wiley.com/10.1002/9780470015902.a0002332.pub3

Apoptosis: Inherited Disorders (Keynote)Helen C Su, Michael J Lenardohttp://doi.wiley.com/10.1002/9780470015902.a0005529.pub3

Intestinal Epithelial Cells: Immu-nological Aspects (Introductory)Andrew W Stadnykhttp://doi.wiley.com/10.1002/9780470015902.a0003816.pub2

ImmunoVision

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ImmunoBooks

Now published by Wiley-Blackwell!Topley & Wilson’s Microbiology and Microbial Infections10th Edition• Available as 8 Volume Set or individual volumes:Volumes 1 and 2: Bacteriology Volumes 3 and 4: Virology Volume 5: Medical Mycology Volume 6: Parasitology Volume 7: Immunology Volume 8: Cumultative Index• For the fi rst time: Online access available in 2010. Visit www.topleyandwilson.com for more information.SET ISBN: 978-0-470-68638-6

AIDS and Tuberculosis: A Deadly LiaisonStefan H. E. Kaufmann, Bruce D. Walker (Eds.) Infection Biology Handbook SeriesISBN: 978-3-527-32270-1

Antiparasitic and Antibacterial Drug Discovery: From Molecular Targets to Drug CandidatesPaul M. Selzer (Ed.) Drug Discovery in Infectious Diseases Book SeriesISBN: 978-3-527-32327-2

The Epigenetics of Autoimmune DiseasesMoncef Zouali (Ed.) ISBN: 978-0-470-75861-8

ImmunoFeature

AIDS and Tuberculosis:

Antiparasitic and Antibacterial Drug

Now published by Wiley-Blackwell!

The Epigenetics of Autoimmune

Biologics for Rheumatoid Arthritis Work, But Which Is Best? Clear Differences Shown in Effi cacy and Adverse Effects

More studies that directly compare the effectiveness of different biologic drugs for rheumatoid arthritis (RA) are needed, say Cochrane Researchers. The researchers reviewed all previous Cochrane Systematic Reviews assessing the effectiveness of biologic disease-modifying drugs for treatment of RA and found that although all were very effective, there was little data on direct comparisons between the drugs that could help doctors decide which to prescribe.Singh JA et al. Cochrane Database of Systematic Reviews 2009, Issue 4. Art. No.: CD007848http://doi.wiley.com/10.1002/14651858.CD007848.pub2

TENS For Osteoarthritis: Not Enough Evidence To Recommend

Despite twenty years of research on the use of electrostimulation techniques (TENS) for treatment of osteoarthritis in the knee, researchers still cannot say whether it reduces pain or physical disability. This is the conclusion of a Cochrane Systematic Review of electrostimulation trials in osteoarthritis.Rutjes AWS et al. Cochrane Database of Systematic Reviews 2009, Issue 4. Art. No.: CD002823http://doi.wiley.com/10.1002/14651858.CD002823.pub2.

New Biologic Drug Is Effective Against Rheumatoid Arthritis

Abatacept, a member of a new class of drug that targets immune cells to treat rheumatoid arthritis (RA), is effective against RA, according to a new Cochrane Systematic Review. The review examines recent trials to assess safety and effi cacy of the drug.Maxwell L and Singh JA. Cochrane Database of Systematic Reviews 2009, Issue 4. Art. No.: CD007277. http://doi.wiley.com/10.1002/14651858.CD007277.pub2.

Exercise Programs Recommended As Standard For Rheumatoid Arthritis

Exercise programs designed to improve strength and stamina are safe and effective treatments for rheumatoid arthritis (RA), according to a new Cochrane Systematic Review. The researchers reviewed dynamic exercise program trials in RA patients and found moderate benefi ts associated with this type of treatment.Hurkmans E et al. Cochrane Database of Systematic Reviews 2009, Issue 4. Art. No.: CD006853.http://doi.wiley.com/10.1002/14651858.CD006853.pub2

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Toll-like receptors – sentries in the B-cell response

Bekeredjian-Ding, I and Jego, G Immunology 2009. 128: 311 – 323.http://doi.wiley.com/10.1111/j.1365-2567.2009.03173.x

NK cells, transplantation and leukemia

Moretta et al.’s review on NK cells discusses new information relating to the molecular basis of successful haploidentical haema-topoietic stem cell transplantation (haplo-HSCT). NK cells are capab-le of killing cancer cells and recent clinical data from haplo-HSCT has revealed NK cells are responsible for highly favourable effects in both adult and paediatric high-risk leukaemias. The authors discuss the role of the HLA class I-specifi c Killer Immunoglobulin-like Receptors (KIR) and alloreactive NK cells in successful haplo-HSCT in patients with high-risk leukaemias.Moretta, A et al. Clin. Exp. Immu-nol. 2009. 157:325 – 331.http://doi.wiley.com/10.1111/j.1365-2249.2009.03983.x

Anti-epidermal growth factor receptor monoclonal antibodies in cancer therapy

On the theme of cancer thera-py, Martinelli et al. discuss the mechanisms of epidermal growth factor receptor (EGFR)-specifi c monoclonal antibodies in cancer therapy. EGFR, a transmemb-rane tyrosine kinase receptor, is the fi rst molecular target against which monoclonal antibodies have been developed for cancer therapy. The authors focus on two recently introduced EGFR mono-clonal antibodies, cetuximab and panitumumab, designed for the treatment of metastatic colorectal and, head and neck cancer.Martinelli, E et al. Clin. Exp. Immu-nol. 2009. 158:1 – 9.http://doi.wiley.com/10.1111/j.1365-2249.2009.03992.x

ImmunoReviews

ImmunoBooks

Contemporary Challenges in AutoimmunityYehuda Shoenfeld, M. Eric Gershwin (Eds.) ISBN: 978-1-57331-762-7

Intracellular Niches of Microbes: A Pathogens Guide Through the Host CellUlrich E. Schaible, Albert Haas (Eds.) ISBN: 978-3-527-32207-7

Sepsis and Non-infectious Syste-mic Infl ammation: From Biology to Critical CareJean-Marc Cavaillon, Christophe Adrie (Eds.) ISBN: 978-3-527-31935-0

An Introduction to Biomedical Science in Professional and Clinical PracticeSarah Jane Pitt, Jim Cunningham ISBN: 978-0-470-05715-5

Bioinformatics for VaccinologyDarren R. Flower ISBN: 978-0-470-02711-0

Bioinformatics for Vaccinology

Sepsis and Non-infectious Syste-

An Introduction to Biomedical Science in Professional

Contemporary Challenges

Intracellular Niches of Microbes:

Translational Mini-review Series: B Cell-Directed Therapies

Translational Mini-Review Series on B Cell-Directed Therapies: Recent advances in B cell-directed biological therapies for autoim-mune disordersM. C. Levesque Clin. Exp. Immunol. 2009. 157:198 – 208.http://doi.wiley.com/10.1111/j.1365-2249.2009.03979.x

Translational Mini-Review Series on B Cell-Directed Therapies: The pathogenic role of B cells in autoantibody-associated autoim-mune diseases – lessons from B cell-depletion therapyM. J. Leandro, I. de la Torre Clin. Exp. Immunol. 2009. 157:191 – 197.http://doi.wiley.com/ 10.1111/j.1365-2249.2009.03978.x

Translational Mini-Review Series on B Cell-Directed Therapies: B cell-directed therapy for autoimmune diseasesC. Hu, F. S. Wong, L. Wen Clin. Exp. Immunol. 2009. 157:181 – 190.http://doi.wiley.com/10.1111/j.1365-2249.2009.03977.x

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Books

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ImmunoVision

Natural Killer cells: acti-vation, killing and disease

NK cells are part of the body’s front line defence against infec-tion and cancer. The September and October issues of Immu-nology feature several reviews discussing recent advances in our understanding of NK cell activati-on, killing, and disease. Due to the potent nature of NK cells their activation must be tightly regulated; Stern-Ginossar & Mandelboim discuss mechanis-ms controlling the expression of the activating receptor NKG2D.Stern-Ginossar, N and Mandel-boim, O Immunology 2009. 128: 1 – 6.http://doi.wiley.com/10.1111/j.1365-2567.2009.03147.x Following activation, NK cell killing is mediated by the release of cytotoxic molecules from secre-tory lysosomes stored within the cell. Topham & Hewitt discuss what we currently know about the molecular mechanisms for NK cell secretory lysosome exocy-tosis, and the immunological consequences of defects within this machinery.Topham, N J and Hewitt, E W Immunology 2009. 128: 7 – 15.http://doi.wiley.com/ 10.1111/j.1365-2567.2009.03123.x

Finally, Culley takes a more global view looking at the function of NK cells in pulmonary infection and infl ammation, specifi cally their contributions to infl uenza, tuberculosis, asthma and chronic obstructive pulmonary disease (COPD).Culley, F Immunology 2009. 128: 151 – 163.http://doi.wiley.com/ 10.1111/j.1365-2567.2009.03167.x

ImmunoVision

6© Wiley-Blackwell 2009

ImmunoBooks

Infections Causing Human CancerHarald zur Hausen Written by the Nobel Prize Laureate in Physiology or Medicine 2008ISBN: 978-3-527-31056-2

Handbook of Therapeutic AntibodiesStefan Dübel (Ed.) ISBN: 978-3-527-31453-9

Bacteriology of Humans: An Ecological PerspectiveMichael Wilson 1st Prize, ‚New Authored Books‘ category, Royal Society of Medicine and Society of Authors Medical Book Awards 2008ISBN: 978-1-4051-6165-7

Viral Oncology: Basic Science and Clinical Applicationsby Kamel Khalili, Kuan-Teh JeangISBN: 978-0-470-37991-2

Bacteriology of Humans:

Viral Oncology: Basic Science

Handbook of

Infections Causing

ImmunoDigest

Tunisian HCV-1b genetic variability: effect on interferon/Ribavirin therapy

In the non-structural protein 5A (NS5A) of hepatitis C virus (HCV), mutations within the interferon sensitivity-determining region (ISDR), the PKR-binding domain (PKR-BD), the variable region 3 (V3), and the interferon/ribavirin resistance-determining region (IRRDR) have been corre-lated with the IFN-based therapy response.

In Tunisia, where a high preva-lence of HCV-1b has been found, no data regarding the implication of NS5A in treatment response were available. In this study, a correlation between the response to the combined interferon/Ribavirin therapy and the genetic variability of Tunisian HCV-1b strains is determined.

Bouzgarrou, N et al. J. Med. Virolo-gy 2009. 81: 2021-2028.http://doi.wiley.com/10.1002/jmv.21641

Clever-1/Stabilin-1 – a multifunctional traffi c light

Immune cell traffi cking between blood and lymphoid organs is essential for the proper function-ing of the immune system. Mechanisms mediating lympho-cyte entrance from the blood into the lymphoid organs and leukocyte traffi cking to sites of infl ammation are well known. In contrast, molecular interactions mediating lymphocyte traffi cking from the periphery via the afferent lymphatics into the draining lymph nodes and their exit from the lymph nodes are poorly characterized.

Karikoski et al. demonstrate that a scavenger molecule, Clever-1/Stabilin-1, mediates traffi cking of lymphocytes to the draining lymph nodes via the afferent lymphatics. The authors also show that targeting infl ammation-induced Clever-1/Stabilin-1 on blood vasculature reduces migra-tion of all leukocyte subtypes to the site of infl ammation. Good news for potential therapeutic application is that despite marked anti-infl ammatory effi cacy, bacte-rial clearance is not signifi cantly compromised by inhibiting Clever-1/Stabilin-1.

Karikoski, M. et al., Eur. J. Immu-nol. 2009. 39: 3477-3487.http://doi.wiley.com/10.1002/eji.200939896

Co-receptor switch during HAART is independent of virological success

The infl uence of antiretroviral therapy on co-receptor tropism remains controversial. To verify if co-receptor tropism shift was affected by HAART, the evolution of proviral DNA V3 genotype after 12 months of a new antiretroviral regimen was compared between responder and non-responder patients.

No association was found bet-ween tropism shift and patient baseline characteristics including age, sex, CDC stage, CD4 count, viral load, exposure and length of previous HAART, enfuvirtide use in the new regimen, number of reverse transcriptase and protease resistance-associated mutations. Conversely, CD4 nadir was corre-lated to emergence of X4 virus in proviral DNA.

The occurrence of a tropism shift in both directions was indepen-dent of HAART use, irrespective of its effi cacy. The CD4 count nadir was the only baseline cha-racteristic able to predict an R5-to-X4 viral shift.

Saracino, A et al. J. Med. Virol. 2009. 81: 2036-2044.http://doi.wiley.com/10.1002/jmv.21598

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ImmunoBooks

Cancer Vaccinesby Ralph M. Steinman (Editor), Kenichiro Hasumi (Editor), Olivera J. Finn (Editor), Jacques Banchereau (Editor)ISBN: 978-1-57331-759-7

Therapeutic Monoclonal Anti-bodies: From Bench to Clinicby Zhiqiang An (Editor)ISBN: 978-0-470-11791-0

The Pulmonary Endothelium: Function in health and disease by Norbert Voelkel, Sharon RoundsISBN: 978-0-470-72361-6

Immunology: Understanding The Immune System, 2nd Editionby Klaus D. ElgertISBN: 978-0-470-08157-0

Cancer Vaccines

Therapeutic Monoclonal Anti-

CD8+LAP+ cells join the Treg Tango!

Regulatory T cells (Treg) are pivo-tal in the maintenance of immune tolerance. Although long recog-nized, CD8+ Treg remain poorly characterized. Chen et al. identify a novel CD8+ Treg population characterized by cell surface ex-pression of the latency–associated peptide (LAP). Unlike other CD8+ Treg, CD8+LAP+ Treg are unique, as they are both TGF-β- and IFN-γ-dependent. It is likely that CD8+LAP+ cells, by producing TGF-β and IFN-γ, establish a regu-latory milieu by which CD8+LAP+ cells facilitate their immunomo-dulatory effects. The identifi cation of CD8+LAP+ cells represents an important step in the investigati-on of Treg populations and may begin to explain unresolved issues in autoimmunity. For example, it is known that IFN-γ-defi cient animals have a more severe form of EAE. Given the fi ndings in this report, this may in part be related to the loss of suppressive capacity of the IFN-γ-dependent CD8+LAP+ Treg.

Chen, M.-L. et al., Eur. J. Immunol. 2009. 39: in presshttp://doi.wiley.com/10.1002/eji.200939441

Human Immunodefi ciency Virus in an Aging Popu-lation, a Complication of Success

By 2015, 50% of HIV-infected in-dividuals in the United States are likely to be aged 50 and older. The rate of progression of untreated HIV disease, response to therapy, and complicating effects of comorbidities differ in older and younger patients. Older untreated patients with HIV demonstrate faster rates of CD4+ cell loss and more rapid progression to acqui-red immunodefi ciency syndrome (AIDS) and death than younger individuals. The treatment of older HIV-infected patients is complicated by preexisting comorbid conditions, including cardiovascular, hepatic, and metabolic complications, which in turn may be exacerbated by the effects of HIV infection per se, modest immunodefi ciency (i.e., at CD4+ counts >350 cells/µL), and the metabolic and other adverse effects of combination antiretro-viral therapy. Nevertheless, older patients derive substantial benefi t from combination antiretroviral therapy despite having less of an immunological response than expected given their adherence to therapy and excellent virological responses.

Kirk, J. B: and Bidwell Goetz, M. J Am Geriatr Soc. 2009. 57: 2129-2138.http://doi.wiley.com/10.1111/j.1532-5415.2009.02494.x

Dengue and the macrophage paradox

Dengue virus is transmitted by mosquitoes and causes a syste-mic infl ammation with high fever that can progress into dengue he-morrhagic fever or dengue shock syndrome. In patients and in mouse models, the virus is most easily detected in macrophages, which are believed to play a key role in establishing and spreading dengue infection in the body.

Fink et al. show, contrary to ex-pectations, depleting macropha-ges in a mouse model of infection leads to an increase in systemic infection. This, together with the observation that macrophages infi ltrate infected lymphoid organs in large numbers, suggests that macrophages play a dual role in dengue infection – while macro-phages are important for establi-shing infection, macrophages are also critical for virus control.

Fink, K. et al., Eur. J. Immunol. 2009. 39: 2809 - 2821http://doi.wiley.com/10.1002/eji.200939389

ImmunoDigest

To fi nd out more about our extensive range

of OnlineBooksTM, visit

www.interscience.wiley.com/

onlinebooks

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Widely read articles

Synthetic lethal targeting of PTEN mutant cells with PARP inhibitorsMendes-Pereira, A. M. et al. EMBO Mol. Med. 2009. 1: 315 – 322http://doi.wiley.com/10.1002/emmm.200900041

Vitamin D and respiratory health Hughes, D. A. and Norton, R. Clin. Expt. Immunol. 2009. 158: 20 – 25http://doi.wiley.com/10.1111/j.1365-2249.2009.04001.x

Flow cytometric in situ proximity ligation analyses of protein interactions and post-translational modification of the epidermal growth factor receptor familyLeuchowius, K. –J. et al., Cytometry A. 2009. 75A: 833 – 839http://doi.wiley.com/10.1002/cyto.a.20771

Toll-like receptors – sentries in the B-cell responseBekeredjian-Ding, I. and Jego, G. Immunol. 2009. 128: 311 – 323http://doi.wiley.com/10.1111/j.1365-2567.2009.03173.x

Studies of cell-mediated immune responses to influenza vaccination in systemic lupus erythematosusHolvast, A. et al., Arthritis Rheum. 2009. 60: 2438 – 2447http://doi.wiley.com/10.1002/art.24679

The cellular and biochemical rules of lipid antigen presentationDe Libero, G. et al., Eur. J. Immunol. 2009. 39: 2648 - 2656http://doi.wiley.com/10.1002/eji.200939425

Gamma/delta T cells are the predominant source of interleukin-17 in affected joints in collagen-induced arthritis, but not in rheumatoid arthritisIto, Y. et al., Arthritis Rheum. 2009. 60: 2294 - 2303http://doi.wiley.com/10.1002/art.24687

Plasmacytoid DC promote priming of autoimmune Th17 cells and EAEIsaksson, M. et al., Eur. J. Immunol. 2009. 39: 2925 - 2935http://doi.wiley.com/10.1002/eji.200839179

Anti-epidermal growth factor receptor monoclonal antibodies n cancer therapyMartinelli, E. et al., Clin. Expt. Immunol. 2009. 158: 1 - 9http://doi.wiley.com/10.1111/j.1365-2249.2009.03992.x

An optimized flow cytometry protocol for analysis of angiogenic monocytes and endothelial progenitor cells in peripheral bloodHristov, M. et al., Cytometry A. 2009. 75A: 848 – 853http://doi.wiley.com/10.1002/cyto.a.20772

IL-17 and IL-22 mediate IL-20 subfamily cytokine production in cultured keratinocytes via increased IL-22 receptor expressionTohyama, M. et al., Eur. J. Immunol. 2009. 39: 2779 - 2788http://doi.wiley.com/10.1002/eji.200939473

Increase in frequency of myeloid-derived suppressor cells in mice with spontaneous pancreatic carcinomaZhao, F. et al., Immunol. 2009. 128: 141 – 149http://doi.wiley.com/10.1111/j.1365-2567.2009.03105.x

Design principles of pluripotencySmith, A. et al., EMBO Mol. Med. 2009. 1: 251 – 254http://doi.wiley.com/10.1002/emmm.200900035

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CD155 and follicular helper T cells

The germinal center reaction required for the production of high affinity and isotype-switched antibodies relies on the presence of follicular helper T (TFH) cells. Peyer’s patches (PP) of the small intestine are permanently immunologically active and har-bor great numbers of TFH cells under steady state conditions. It has been recently shown that the IgSF family member CD155 participates in the generation of gut humoral responses. Seth et al. provide a plausible explanation for this finding by demonstrating that CD155-deficient mice harbour significantly reduced TFH cell numbers in the PP. This defect affects only the TFH cells and not Th1 or Th2 cells.

Although the exact contribution of CD155 in TFH life cycle remains to be elucidated, this study sheds some light into the mechanisms by showing that only TFH cells down-regulate the expression of the CD155 ligand CD226, and replaces this agonists by the pu-tative inhibitory CD155 counter-receptor TIGIT/WUCAM.Seth, S. et al., Eur. J. Immunol. 2009. 39: 3160 - 3170http://doi.wiley.com/10.1002/eji.200939470

A New Paradigm in the Detection of Acute Renal Allograft Rejection

The pursuit of a noninvasive methodology for the detection of acute renal allograft rejection has received a boost from a unique collaboration between transplant surgeons and engineers. Brown and colleagues have applied Ra-man spectroscopy (RS) to charac-terize differences between activati-on states of the primary immune mediator of acute rejection (AR), the T-lymphocyte. By utilizing this laser-based technology, which is capable of resolving and quan-tifying material at a molecular level, specific cell-surface receptor arrays can be analyzed yielding unique spectral signatures.

This group has previously demonstrated the ability of RS to differentiate activated from non-activated T-lymphocytes with high sensitivity. In the current article, the authors tackle the notion of specificity, reporting on key signature differences between T-lymphocyte groups activated by alloreactive versus CD3/CD28 stimuli. This research forms the foundation for further investiga-tion into a rapid diagnostic tool for the detection of AR that can be translated quickly to the clinical setting.

Brown, K. L. et al. Cytometry A 2009. 75: 917-923http://doi.wiley.com/10.1002/cyto.a.20797

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