Disappearance of specifically mlc-responsive lymphocytes in cba mice injected with cells from the h-2-compatible, m-antigen-incompatible strain c3h.

The mixed lymphocyte culture (MLC) response of lymphocytes from CBA mice injected with spleen cells from the H-2-compatible strain C3H was studied. The response of CBA lymphocytes against C3H cells was higher than that obtained against H-2-disparate strains. Intravenous injection of C3H cells resulted in a markedly increased MLC response in lymph nodes but not in the thymus during the first 1 to 3 days. Thereafter, the specific MLC response decreased drastically, far below that of nonimmunized animals. Reactivity was back to normal in the thymus after approximately 4 weeks but remained suppressed in lymph nodes for more than half a year. A decreased response was also noted in spleen, Peyer's patches, and the peripheral blood lymphocyte population. Such a state of relative unresponsiveness was achieved by injecting as few as 10-4 C3H spleen cells. This exhaustion of the specific MLC response could not be explained by production of blocking serum factors or of cells that can inhibit the MLC response. The strong MLC response obtained by lymphocytes from nonimmunized animals may be due to disparity at the newly detected M locus. This antigenic system is characterized by strong MLC stimulatory capacity and no detectable production of humoral antibodies or development of effector cells capable of killing M-antigen-bearing cells. A possible explanation of the results is that the CBA mice become chimaeric for a long time after injection of C3H cells. This prolonged exposure to a foreign transplantation antigen may lead to exhaustion of the specifically responsive lymphocytes.