Distinct cytokine-driven responses of activated blood gammadelta T cells: insights into unconventional T cell pleiotropy.
Human Vgamma9/Vdelta2 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 alphabeta T cells provoked us to apply cDNA microarrays to explore the potential pleiotropy of HMB-PP-activated Vgamma9/Vdelta2 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 alphabeta 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 gammadelta 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 gammadelta 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 Vgamma9/Vdelta2 TCR agonists.
Vermijlen
David
D
Peter Gorer Department of Immunobiology, Guy's, King's and St. Thomas' Medical School, King's College London, London, UK.
Ellis
Peter
P
Langford
Cordelia
C
Klein
Anne
A
Engel
Rosel
R
Willimann
Katharina
K
Jomaa
Hassan
H
Hayday
Adrian C
AC
Eberl
Matthias
M
D002478:Cells, Cultured; D054382:Chemokine CXCL13; D019743:Chemokines, CXC / Q000032:analysis / Q000235:genetics; D016207:Cytokines / Q000494:pharmacology*; D011756:Diphosphates / Q000494:pharmacology; D020869:Gene Expression Profiling; D006801:Humans; D007109:Immunity / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis; D013601:T-Lymphocytes / Q000737:chemistry / Q000187:drug effects* / Q000276:immunology*
C443995:4-hydroxy-3-methylbut-2-enyl pyrophosphate; C110663:CXCL13 protein, human; D054382:Chemokine CXCL13; D019743:Chemokines, CXC; D016207:Cytokines; D011756:Diphosphates; D016692:Receptors, Antigen, T-Cell, gamma-delta