Mutual tolerization of histoincompatible lymphocytes.

T lymphocytes react strongly against foreign major histocompatibility complex encoded class I antigens by destroying incompatible tissue in vivo, and by generating cytotoxic T lymphocytes (CTL) in vitro. The absence of reactivity against self antigens may be due to clonal deletion of self-reactive T cells during their ontogeny in the thymus. The functional clonal deletion of mature T cells in the periphery was described recently: CTL recognizing antigen on other CTL are eliminated (Rammensee et al., Immunol. Today 1985. 6: 41). Hence, in a normal immune system only autoreactive cells would be eliminated. Here we show that injection of lymphocytes into class I-incompatible mice leads to abrogation of host anti-donor as well as donor anti-host reactivity, leaving a mixed population of host and donor T cells reactive against third-party antigens. The results demonstrate the existence of a peripheral failsafe mechanism for the elimination of autoaggressive CTL. Whether this failsafe mechanism is actually used under physiological conditions is a different question.