Haplotype-specific suppressor T cells mediating linked suppression of immune responses elicited by third-party H-2 alloantigens

Abstract

Specific suppressor T cells (Ts) were induced in vitro by incubation of mouse spleen/lymph node cells with allogeneic heat-treated cells. These Ts inhibit mixed lymphocyte reaction (MLR) in a haplotype-specific manner. Ts also suppress cell proliferation induced by third-party H-2 alloantigens provided these are expressed on the same cell surface as at least some of the H-2 antigens used for Ts activation. Ts activated by H-2 plus non-H-2 alloantigens suppress an MLR induced by irrelevant H-2 alloantigens if these are expressed on the same cell surface as the non-H-2 alloantigens used for Ts activation. Products of the H-2 region or non-H-2 alloantigens which are not able to stimulate cell proliferation do not activate Ts. These Ts are first demonstrable after 4 days of incubation of lymphoid cells with heat-treated allogeneic cells and they inhibit MLR only if added at the very beginning of the culture. Exogenous interleukin 2 does not overcome suppression and the suppression is not due to a cytotoxic effect, since heat-treated cells do not elicit cell proliferation or cytotoxic cells. Moreover, the specific Ts differ in their Thy-1+,Ly-1+,2-phenotype from Ly-2+ allospecific cytotoxic cells. Thus specific Ts could be induced in vitro, which demonstrate linked suppression for third-party H-2 alloantigens provided these are expressed on the same cell surface as the antigens used for Ts activation.