The primary response of human gamma/delta + T cells to Mycobacterium tuberculosis is restricted to V gamma 9-bearing cells.
We have previously reported that peripheral blood gamma/delta + T cells proliferate in high frequency (1 in 2-20) in response to heat-killed Mycobacterium tuberculosis (M.tb.). In the present study, the T cell receptor phenotype of mycobacteria-responsive human gamma/delta + T cells was analyzed in primary cultures with a set of monoclonal antibodies (mAbs) directed against V gamma 9, V delta 1, and V delta 2. When unseparated T cells were stimulated with M.tb., all proliferating gamma/delta + T cells expressed V gamma 9 (and V delta 2) after culture. Selective depletion of V gamma 9-bearing cells before culture completely abolished the proliferative response of all gamma/delta + cells (but did not inhibit reactivity of alpha/beta + T cells). In addition, when CD4- CD8- thymocytes were stimulated with M.tb., there was again selective outgrowth of V gamma 9+ cells. In this case, the starting responder population contained few (0.5-1.8%) V gamma 9+ and many (11.5-31.5%) V delta 1+ cells that did not coexpress V gamma 9. These V delta 1+ cells were not activated by M.tb. but could be readily stimulated by anti-V delta 1 mAb A13. Finally, a V gamma 9-specific mAb selectively suppressed the proliferative response of gamma/delta + T cells to M.tb. Taken together, our results demonstrate that, within gamma/delta + T cells, reactivity towards M.tb. is an exclusive property of V gamma 9+/V delta (2+)-bearing cells.
Kabelitz
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D
Institut für Immunologie, Universität Heidelberg, FRG.
Bender
A
A
Prospero
T
T
Wesselborg
S
S
Janssen
O
O
Pechhold
K
K
D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000032:analysis; D005434:Flow Cytometry; D006801:Humans; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D016692:Receptors, Antigen, T-Cell, gamma-delta; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D011948:Receptors, Antigen, T-Cell; D016692:Receptors, Antigen, T-Cell, gamma-delta