Activation and activation-driven death of human gamma/delta T cells.
We have concentrated on three functional aspects of human gamma/delta+ T cells. (1) Peripheral blood gamma/delta+ T cells proliferate at a high frequency in response to heat-killed mycobacteria (M.tb.). We present evidence that the primary response of human gamma/delta+ T cells is restricted to those cells bearing a V gamma 9/V delta 2 receptor. (2) T cells expressing the alpha/beta TCR can be activated through the CD2 antigen via an "alternative" pathway. Activation requires the combined signaling of 2 mAb directed against two distinct epitopes of CD2. In striking contrast, cloned gamma/delta+ T cells are activated by a single immobilized anti-CD2 mAb directed against the sheep E-binding epitope of CD2. Stimulation of cloned gamma/delta+ T cells by a single anti-CD2 mAb results in IL-2 production, proliferation, and triggering of cytolytic effector function. (3) Cloned gamma/delta+ T cells are susceptible to programmed cell death (apoptosis) when stimulated simultaneously by anti-CD3/TCR mAb plus exogenous IL-2. The very same clones are activated, however, by the same stimuli in the absence of exogenous IL-2 (but in the presence of LCL feeder cells). This provides the basis for a model where extensive gamma/delta+ T cell proliferation is negatively regulated by antigen plus IL-2.
Institut für Immunologie, Universität Heidelberg, Mannheim, Germany.
D
D
Kabelitz
K
K
Pechhold
A
A
Bender
S
S
Wesselborg
D
D
Wesch
K
K
Friese
O
O
Janssen
D000911:Antibodies, Monoclonal / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D018801:CD2 Antigens; D002470:Cell Survival / Q000187:drug effects; D005786:Gene Expression Regulation; D015658:HIV Infections / Q000097:blood / Q000276:immunology; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D007958:Leukocyte Count; D008213:Lymphocyte Activation; D009161:Mycobacterium / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis / Q000235:genetics; D016692:Receptors, Antigen, T-Cell, gamma-delta; D011971:Receptors, Immunologic / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D016692:Receptors, Antigen, T-Cell, gamma-delta; D011971:Receptors, Immunologic