The regulatory role of I-J subregion in neonatal tolerance induction to H-2D alloantigens.

The mechanism of neonatally induced transplantation tolerance was studied in two mouse strain combinations involving differences at the D region of the H-2 complex only or at the same D region plus I-J subregion (including I-E, I-C, S and G regions). In the strain combination with the H-2D difference only, cells from tolerant mice proliferated markedly in the MLR assay when incubated with antigens tolerated in vivo, whereas the MLR reactions were negative in the combination with D plus I-J region disparities. In the latter combination cells from tolerant mice also did not respond to third-party antigens and their incubation with the tolerated antigens led to the suppression of cell proliferation. This non-specific suppression was absent in cells from tolerant mice in the strain combination, which differed in I-C, S, G and D alloantigens. Specific suppressor cells, which inhibited the development of cytotoxic cells, were demonstrated in tolerant mice of both strain combinations. The results show that, in additon to the specific suppressor cells induced by H-2K or H-2D alloantigens, nonspecific suppressor cells induced by the I-J region disparity that may regulate the resultant activity against H-2D (and probably also H-2K) alloantigens are involved in transplantation tolerance.