Regulation of cell-mediated immunity in cryptococcosis. I. Induction of specific afferent T suppressor cells by cryptococcal antigen.

By injecting cryptococcal antigen i.v. into CBA/J mice, we have simulated a level of antigenemia that is known to occur naturally in murine and human cryptococcosis. The cryptococcal antigen induced a population of lymph node (LN) cells that, upon adoptive transfer, could specifically suppress the delayed-type hypersensitivity (DTH) response to cryptococcal antigen and the splenic T lymphocytes responsible for in vitro inhibition of growth of Cryptococcus neoformans. The cryptococcal-antigen-induced suppressor cell could be detected in the LN as early as 5 days and was still in significant numbers 7 days after antigen injection. Suppressor cells were not found in the spleens of tolerized mice, nor could serum from these animals adoptively transfer suppression. The suppressor cells in this model were shown to be T lymphocytes, which exerted their effect on the afferent limb of the DTH response; therefore, they were similar to the Ts1 cell in the ABA-DTH, NP-DTH, and NP cutaneous sensitivity models and to the afferent suppressor cells in the DNFB contact sensitivity system. The percent suppression of the cryptococcal DTH response was dependent on the amount of antigen injected. Approximately, 35 micrograms of cryptococcal antigen per ml of serum was sufficient to induce significant suppression of the cell-mediated immune response.