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 allogenic 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 x BALB/c)F1 mice suppressively primed against B10.A(5R) cells (directed against JkEk antigens), when adoptively transferred to normal syngeneic recipients, were capable of suppressing the hosts' DTH response to B10.A(4R) cells (KkAk antigens) when the recipients were challenged with [B10.A(4R) x B10.A(5R)]F1 cells (KkAk x JkEk). The recipients express normal DTH reactivity to B10.A(4R) cells when challenged with a mixture of B10.A(4R) cells (KkAk + JkEk). 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.
D000818:Animals; D000939:Epitopes; D006183:H-2 Antigens / Q000235:genetics*; D006968:Hypersensitivity, Delayed / Q000276:immunology*; D007116:Immunization, Passive; D007519:Isoantigens / Q000276:immunology; D008285:Major Histocompatibility Complex; D051379:Mice; D008805:Mice, Inbred A; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D014176:Protein Biosynthesis; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D000939:Epitopes; D006183:H-2 Antigens; D007519:Isoantigens