DIFFERENTIAL EXPRESSION OF HELPER VERSUS EFFECTOR ACTIVITY IN MICE RENDERED NEONATALLY TOLERANT OF CLASS II MHC ANTIGENS

Abstract

Since tolerogen-specific helper activity is present in MLR-positive class II MHC tolerant mice, a loss of helper activity is unlikely to be responsible for he maintenance of tolerance in these mice. An alternative hypothesis, that effector cell function is selectively downregulated, has been examined with lymphocytes from MLR-positive class-II MHC tolerant mice on both the A strain and the B10 background. The results demonstrate that lymphocytes from A-strain-tolerant mice were unable to generate tolerogen-specific effector cells in any of the assays tested (CML with or without exogenous growth factor and DTH following in vivo priming or local adoptive transfer), even though these mice possess tolerogen-responsive T helper cells. In contrast, a majority of MLR-positive tolerant mice on the B10 background generated measurable tolerogen-specific cytotoxic activity in the absence of exogenous growth factor, and all the mice examined generated substantial cytotoxic activity in the presence of exogenous growth factor. However, in a local adoptive transfer reaction, lymphocytes from these mice failed to display DTH. It is concluded that tolerance is maintained by selective impairment of class II specific effector functions and that regulation of DTH rather than CTL activity may be central to maintenance of in vivo tolerance to class II MHC antigens.