Correlation of intrathymic tolerance with intrathymic chimerism in neonatally tolerized mice.

T cell tolerance to alloantigens can be induced in neonatal mice by the injection of semiallogeneic adult spleen cells. The thymus of neonatally injected mice rapidly becomes specifically unresponsive to the alloantigens expressed by the injected cells, even though the level of chimerism in the thymus of such mice is reportedly marginal compared with that of the periphery. In this report, we have studied the immune reactivity and degree of chimerism in the thymuses of 24 neonatally injected mice. In 13 older mice, the proliferative response of the thymocytes from individual mice to the injected alloantigen varied from strong reactivity to complete tolerance. Interestingly, analysis by flow microfluorometry of the same thymocytes for the presence of the inoculated alloantigen revealed an inverse correlation. That is, the thymuses which had a greater degree of chimerism were tolerant and those with fewer or no detectable cells were partially or totally reactive. The thymuses of 11 younger neonatally injected mice were invariably tolerant to both the MHC and Mls alloantigens of the F1 inocula. Analysis by flow microfluorometry of the thymocytes of these mice revealed that significant numbers of F1 cells reside in the thymuses of mice injected as neonates with semiallogeneic cells. These cells represent a possible source of specific tolerogen for thymocytes during their intrathymic differentiation.