GAMMA-DELTA-T-CELLS DIFFERENTIATE INTO A FUNCTIONAL BUT NONPROLIFERATIVE STATE DURING A NORMAL IMMUNE-RESPONSE

To obtain a homogeneous population of gammadelta T cells to investigat e their role in an immune response, we have made a scid mouse doubly t ransgenic for rearranged gamma and delta genes. The receptor (KN6) enc oded by these genes is specific for the major histocompatibility compl ex class I protein encoded by the T22b gene. This mouse contains high levels of transgenic gammadelta T cells in the spleen and thymus and n o other T lymphocytes. Immunization of these KN6-scid (H-2d, TL(d)) mi ce with 10(7) C57BL/6J (abbreviated B6) (H-2b, TL(b)) Spleen cells res ulted in proliferation and activation of the gammadelta T cells in spl een and clearing of the allogeneic B6 lymphocytes. Subsequently, the m ajority of activated cells died by apoptosis and the remaining cells w ere anergic with regard to proliferation. The anergic cells did not re spond to restimulation by B6 spleen cells in vitro or in vivo, and add ition of exogenous interleukin 2 failed to restore the response to B6 cells. Cytotoxicity, a property of KN6+ cells during a primary stimula tion, was no longer detectable in the proliferatively anergic cells. H owever, B6 spleen cells injected into mice primed 12 days previously w ere cleared with a much greater efficiency than on primary challenge a nd in an antigen-specific manner. We conclude that after exposure to a ntigen, gammadelta T cells rapidly proliferate into blasts; the majori ty of the blasts rapidly die, with the nonproliferating cells remainin g in a highly active state for several weeks and able to initiate elim ination of lymphoid cells bearing the TL(b) epitope.