Antigen‐specific suppression of human antibody responses by allogeneic T cells II. Cell interactions involved in the generation of suppression

Abstract

Specific antibody responses to influenza virus were obtained in vitro from human blood mononuclear cells (PBMC). Antibody production in these cultures was profoundly suppressed by the addition of allogeneic T cells with the surface phenotype Leu2a+ (CD8+), Leu8-. Suppression by allogeneic T suppressor (Ts) cells required interactions only between T-depleted B (E-) cells and allogeneic Leu2a+. No evidence was obtained for T-T cell interactions, or for Ts inducer cells similar to those described for nonspecific antibody responses to pokeweed mitogen. Moreover, allogeneic E+, or allogeneic Leu2a+ cells were able to suppress specific antibody responses by E- cells when help was provided by T cell-replacing factor showing that the target of suppression was the responding E- cells, and not T helper cells. In contrast to allogeneic T cells, allogeneic E- cells did not suppress antibody production when added to cultures of unfractionated PBMC (E- + E+). That is, Ts cells activated to allogeneic E- were unable to suppress antibody production by the syngeneic E- cells present in the same culture tube. This result shows that alloactivated Ts cells were specific for the allogeneic E- target cells, and that suppression was not mediated by nonspecific allogeneic effects. Allogeneic Ts cells therefore differ from Ts cells in pokeweed mitogen responses by their specificity, and by their activation in the absence of Ts inducer cells.

Characterisation of Cyclosporine-Induced Suppressor Cells in Murine Delayed-Type Hypersensitivity Responses

“…Others have ob served similar Ly2+ suppressor T cells in the regula tion of antibody production [23], DTH [24] and cyto toxicity [25]. Alloreactive T cells have been shown to suppress in vitro antibody responses by human lym phocytes in an antigen-specific manner, implying that alloreactive suppression is mediated by antigen-spe cific or possibly idiotype-specific T suppressor cells [26][27][28]. The data presented here demonstrate that cel lular responses to alloantigens are also controlled by Ly2+ suppressor T cells, and this may be one mech anism for CsA-induced prolongation of allograft sur vival and the suppressive effect of CsA on the induc tive phase of autoimmune diseases.…”