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T Cells: Insights into Unconventional T Cell Pleiotropy1
,¶,¶,||
* Peter Gorer Department of Immunobiology, King’s College London, London, United Kingdom;
Institute for Medical Immunology, Université Libre de Bruxelles Gosselies, Belgium;
The Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom;
Biochemisches Institut, Infektiologie, Justus-Liebig-Universität Giessen, Giessen, Germany;
¶ Institut für Klinische Chemie und Pathobiochemie, Universitätsklinikum Giessen und Marburg, Giessen, Germany; and
|| Institute of Cell Biology, University of Bern, Bern, Switzerland
Human V
9/V
2 T cells comprise a small population of peripheral blood T cells that in many infectious diseases respond to the microbial metabolite, (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP), expanding to up to 50% of CD3+ cells. This "transitional response," occurring temporally between the rapid innate and slower adaptive response, is widely viewed as proinflammatory and/or cytolytic. However, increasing evidence that different cytokines drive widely different effector functions in 
T cells provoked us to apply cDNA microarrays to explore the potential pleiotropy of HMB-PP-activated V9/V2 T cells. The data and accompanying validations show that the related cytokines, IL-2, IL-4, or IL-21, each drive proliferation and comparable CD69 up-regulation but induce distinct effector responses that differ from prototypic T cell responses. For example, the Th1-like response to IL-2 also includes expression of IL-5 and IL-13 that conversely are not induced by IL-4. The data identify specific molecules that may mediate T cell effects. Thus, IL-21 induces a lymphoid-homing phenotype and high, unexpected expression of the follicular B cell-attracting chemokine CXCL13/BCA-1, suggesting a novel follicular B-helper-like T cell that may play a hitherto underappreciated role in humoral immunity early in infection. Such broad plasticity emphasizes the capacity of T cells to influence the nature of the immune response to different challenges and has implications for the ongoing clinical application of cytokines together with V9/V2 TCR agonists.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by a Marie-Curie Intra-European Fellowship (to D.V.) and by grants from The Wellcome Trust (to A.C.H.), the Deutsche Forschungsgemeinschaft (to H.J.), and the Else Kröner-Fresenius Stiftung (to M.E.).
2 Address correspondence and reprint requests to Dr. Adrian C. Hayday, Peter Gorer Department of Immunobiology, Guy’s, King’s and St. Thomas’ Medical School, King’s College London, London SE1 9RT, U.K. E-mail address: adrian.hayday{at}kcl.ac.uk
3 Current address: Department of Medical Biochemistry and Immunology, Cardiff University School of Medicine, Cardiff CF14 4XN, U.K.
4 Abbreviations used in this paper: TFH cell, follicular B-helper-like T cell; GC, germinal center; HMB-PP, (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate; c, common -chain; DC, dendritic cell; FDC, follicular DC; LN, lymph node; LT, lymphotoxin; aRNA, antisense RNA.
5 The online version of this article contains supplemental material.
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