Collaboration between in vivo responses to LD and SD antigens of major histocompatibility complex

Abstract

STUDIES using mixed leukocyte culture (MLC) and cell mediated lympholysis (CML) tests, have suggested a possible differential role for LD and SD antigens associated with the major histocompatibility complex (MHC, H–2 in mouse) in allograft reactions^1–3. LD differences are primarily responsible for stimulating the proliferative response in MLC; the SD antigens are the major targets in CML¹. The presence of LD differences on the stimulating cell in MLC enhances the cytotoxic response against the SD antigens. The cellular basis for this potentiation of CML is that two separate subpopulations of T lymphocytes are differentially reactive to LD and SD antigens^1,3–5. A proliferating helper cell responds primarily to LD differences whereas cytotoxic T lymphocytes are more strongly activated by the SD antigens. Lafferty et al.⁷ and Talmage et al.¹⁰ have shown that allogeneic thyroids transplanted under the kidney kapsule are rejected less rapidly if they are first cultured in vitro. Injection of peritoneal exudate cells from the thyroid donor into the recipient speeds up rejection. They suggest that the peritoneal exudate cells sensitise the recipient and that the sensitised cells can invade and reject the thyroid. A further refinement in the interpretation of their data might suggest that either in addition to the mechanism they propose or as an alternative to it the peritoneal exudate cells provide an LD stimulus to the recipient's proliferating helper T cells, and that these cells either by themselves or through a secreted helper factor potentiate the development of cytotoxic T lymphocytes directed at the SD antigens on the graft. Our experiments reported here are consistent with this model.