Distinct Cytokine-Driven Responses of Activated Blood γδ T Cells: Insights into Unconventional T Cell Pleiotropy
| Autor: | Anne Klein, David Vermijlen, Hassan Jomaa, Matthias Eberl, Katharina Willimann, Cordelia Langford, Peter R. Ellis, Adrian Hayday, Rosel Engel |
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| Rok vydání: | 2007 |
| Předmět: |
T-Lymphocytes
T cell Immunology Biology Article Interleukin 21 medicine Humans Immunology and Allergy Cytotoxic T cell IL-2 receptor Antigen-presenting cell Cells Cultured Oligonucleotide Array Sequence Analysis Gene Expression Profiling ZAP70 Immunity Receptors Antigen T-Cell gamma-delta Natural killer T cell Acquired immune system Chemokine CXCL13 Cell biology Diphosphates medicine.anatomical_structure Cytokines Chemokines CXC |
| Zdroj: | The Journal of Immunology. 178:4304-4314 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | Human Vγ9/Vδ2 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 αβ T cells provoked us to apply cDNA microarrays to explore the potential pleiotropy of HMB-PP-activated Vγ9/Vδ2 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 αβ 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 γδ 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 γδ 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 Vγ9/Vδ2 TCR agonists. |
| Databáze: | OpenAIRE |
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