Suppressor T-cell activity in MRL/Mp- lpr/lpr mice: Differential effects on primary and memory antibody responses of MRL/Mp- lpr/lpr and MRL/Mp-+/+ spleen cells to thymus dependent and thymus independent antigens in vitro

Abstract

We have previously shown that suppressor-T-cell (T s) activity in the spleens of autoimmune MRL/Mp- lpr/lpr (MRL/l) mice is increased after 2 months of age. The T s suppress the in vitro primary IgM response to the thymus-dependent (TD) antigen sheep erythrocytes (SRBC) of B and T cells from young congenic MRL/Mp +/+ (MRL/n) mice which lack the lymphoproliferation ( lpr) gene. The T s are nylon wool nonadherent, Thy 1.2 positive, and radiation sensitive. The studies presented here were done to further characterize the T s and to attempt to determine the mechanism of action of these cells. We found that increased T s activity was also present in the proliferating lymph nodes of old MRL/l mice but not in lymph nodes of young MRL/l or MRL/n mice. The splenic T s equally suppressed the primary IgM SRBC response of both young MRL/l and MRL/n B and T cells, indicating that MRL/l SRBC-specific B and T cells are not resistant to suppression. The IgM response of MRL/n B and T cells to the T-independent (TI) antigen trinitrophenyl conjugated to Brucella abortus (TNP-BA) was not suppressed by the T s, although the IgM response to TNP was suppressed when TNP was coupled to the TD carrier SRBC. The results of kinetics studies of T s expression showed that when the T s were added on Day 0 of culture the SRBC response was suppressed as early as Day 2 of culture; however, when the T s were added on Days 1, 2, or 3 of culture, the suppression was reduced. The T s suppressed the in vitro memory IgG response of spleen cells from MRL/n mice which had been primed with SRBC; the memory IgG responses of spleen cells from MRL/l mice were variably suppressed. Taken together, these results suggest that the T s suppress T H function in early events of antibody production and that some activated B or T cells may be resistant to the effects of the T s. Increased T s activity was not present in the spleens of aged New Zealand Black X NZ White (NZB/W) F 1 mice. Possible reasons for the presence of increased T s activity in MRL/l mice and its relation to autoimmune disease is discussed.