Lympho-stromal interactions in the thymus: medullary thymocytes react with I-A determinants on autochthonous thymic stimulator cells.

Abstract

AbstractPrimary (1o) and secondary (2o) syngeneic mixed lymphocyte culture (SMLC) reactions in autochthonous murine thymus cell cultures (peanut agglutinin‐unreactive) or syngeneic mixed thymus‐spleen cell cultures were studied. The 1o thymic SMLC responder cells were Thy‐1+, Lyt‐1+, Lyt‐2−. The 1o thymic syngeneic mixed lymphocyte reaction (SMLR) could be inhibited with monoclonal antibodies directed against determinants Ia.m1 and Ia.m6, in the absence of complement.Positive selection of thymic SMLC cells from 1o cultures was achieved by enriching reactive lymphoblasts on discontinuous Percoll density gradients. The 2o memory populations were obtained by allowing the selected lymphoblasts to revert back to small resting 2o cells in the absence of SMLC stimulation. The thymic 2o SMLC populations were highly enriched in their activity and were almost exclusively specific for self stimulator cells.The 2o thymic SMLC cells were found to be Thy‐1+, membrane immunoglobulin‐negative, H‐2K/D+, I‐A−, I‐E− and I‐J−. They were hardly lysed by anti‐Lyt‐1 antibodies and not at all lysed by monoclonal antibodies detecting Qat‐4 and 5, and Lyt‐2 antigens, in the presence of complement. Stimulator cells were found in fast‐sedimenting or low‐density fractions of thymus. They expressed H‐2K/D, I‐A‐, and I‐E antigens but lacked membrane immunoglobulin and Thy‐1. Not all I region determinants seemed to be of equal importance in the 2o thymic SMLC: I‐A subregion compatibility between responding and stimulating cells was a minimal requirement for the induction of 2o thymic SMLC responses. Although several relevant anti I‐region antibodies reacted with the stimulator cells in the presence of C, these and other anti‐Ia antibodies varied considerably in their capacity to block 1o and 2o autochthonous thymic SMLR in the absence of complement.Our finding that the thymus contains the responder as well as the stimulator cells capable of interacting in an autochthonous proliferative reaction will be discussed with regard to its implications for the intrathymic differentiation of T lymphocytes.