In vivo treatment of neonatal mice with anti-I-A antibodies interferes with the development of the class I, class II, and Mls-reactive proliferating T cell subset.

Abstract

In this study we investigated the effect of monoclonal anti-I-A Ab treatment of neonatal mice on the development of alloreactive class I-specific, class II-specific, and Mls-specific T cell proliferative responses. Responses to both class I and class II alloantigens, as well as to Mls antigens, were nearly abrogated at the end of the 2- to 3-wk in vivo treatment period in both the thymus and the spleen. Development of suppressor cells could be excluded as the cause of the observed defect. Diminished responsiveness could not be restored by the addition of IL 2-containing supernatant, suggesting that the reduced T cell proliferative response in anti-I-A-treated mice is due to defective or absent MHC-specific T cell precursors. Furthermore, generation of alloreactive class I-specific proliferative responses was dependent on self-class II recognition, thus providing an explanation for the absence of class I-specific proliferating T cells. Finally, a non-Ia-restricted T cell response, i.e., Con A-induced proliferation, was not affected by anti-I-A Ab treatment. It was previously reported that neonatal anti-Ia Ab treatment results in reduced Ia-antigen expression in the thymus, and that the development of the class I-specific CTL precursors proceeds undisturbed in these mice. The present results extend these findings and suggest that in vivo development of class II-restricted T cells is dependent on interaction with Ia-encoded products on cells either in the thymus or at other sites where T cells undergo development. Moreover, these results demonstrate that in vivo development of the alloreactive class II-specific T cell repertoire is dependent on development of self-class II recognition.