Mechanisms of Vdelta1 gammadelta T cell activation by microbial components.
There are two major subsets of gammadelta T cell in humans. Vgamma2Vdelta2 T cells predominate in the circulation and significantly expand in vivo during a variety of infectious diseases. Ags identified for the Vdelta2 T cells are nonpeptide phosphate, amine, and aminobisphosphonate compounds. In contrast, Vdelta1-encoded TCRs account for the vast majority of gammadelta T cells in tissues such as intestine and spleen. Some of these T cells recognize CD1c and MHC class I-related chain (MICA/B) molecules [correction]. These T cells are cytotoxic and use both perforin- and Fas-mediated cytotoxicity. A fundamental question is how these gammadelta T cells are activated during microbial exposure to carry out effector functions. In this study, we provide evidence for a mechanism by which Vdelta1 gammadelta T cells are activated by inflammatory cytokines in the context of the Vdelta1 TCR. Dendritic cells are necessary as accessory cells for microbial Ag-mediated Vdelta1 gammadelta T cell activation. Cytokine (IL-12), adhesion (LFA3/CD2, LFA1/ICAM1) and costimulatory (MHC class I-related chain (MICA/B) molecules/NK-activating receptor G2D) molecules play a significant role along with Vdelta1 TCR in this activation.
Das
Hiranmoy
H
Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Sugita
Masahiko
M
Brenner
Michael B
MB
D017951:Antigen Presentation; D018968:CD58 Antigens / Q000502:physiology; D002460:Cell Line; D003713:Dendritic Cells / Q000502:physiology; D006090:Gram-Negative Bacteria / Q000276:immunology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology; D018664:Interleukin-12 / Q000502:physiology; D008213:Lymphocyte Activation; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis*; D011971:Receptors, Immunologic / Q000502:physiology; D055607:Receptors, Natural Killer Cell; D013601:T-Lymphocytes / Q000276:immunology*
D018968:CD58 Antigens; D016692:Receptors, Antigen, T-Cell, gamma-delta; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; D018799:Intercellular Adhesion Molecule-1; D018664:Interleukin-12