Regulation of delayed-type hypersensitivity. VII. The role of I-J subregion gene products in the inhibition of delayed-type hypersensitivity to major histocompatibility antigens by specific suppressor T cells

Suppressor T cells for delayed-type hypersensitivity (DTH) to alloantigens are induced by injecting mice intravenously with a high dose of X-irradiated allogeneic cells. Using the same protocol, suppression of DTH directed against H-2 subregion products could also be induced, provided that the H-2 incompatibility between the cells used for the induction of suppression and the recipients includes the I-J subregion genes. Thus, the I-J subregion difference is both necessary and sufficient for the induction of suppression of DTH to the whole or part of the H-2 gene products. The suppression appears to be mediated by antigen-specific suppressor T cells which recognize the allo-I-J molecules and are able to suppress the DTH response to other H-2 subregion gene products in an associative recognition manner. T cells from (B10 × BALB/c)F₁ mice suppressively primed against B10.A(5R) cells (directed against J^kE^k antigens), when adoptively transferred to normal syngeneic recipients, were capable of suppressing the hosts' DTH response to B10.A(4R) cells (K^kA^k antigens) when the recipients were challenged with [B10.A(4R) × B10.A(5R)]F₁ cells (K^kA^k × J^kE^k). The recipients express normal DTH reactivity to B10.A(4R) cells when challenged with a mixture of B10.A(4R) and B10.A(5R) cells (K^kA^k + J^kE^k). These results provide direct evidence that when functioning as alloantigens, the I-J determinants preferentially induce suppressor T cells which specifically impair the immune response to the I-J molecules as well as other H-2 gene products if they are physically associated with the I-J determinants. The role of I-J subregions as the suppressor genes is discussed in terms of the possible application in transplantation immunity and the host's defence against infectious diseases.