Immune response to Cryptococcus neoformans soluble polysaccharide: immunological unresponsiveness.

Mice injected with 100 to 800 microgram of Cryptococcus neoformans soluble polysaccharide showed a reduced ability to produce antibody after a challenge immunization with polysaccharide emulsified in Freund incomplete adjuvant. These animals were considered immunologically unresponsive. Animals given an initial injection of 25 or 50 microgram of polysaccharide responded to a challenge immunization in the same manner as control animals. Reversion of unresponsive mice to antibody production without further antigenic stimulation did not occur during a 12-week experimental period. These animals exhibited a partial response to challenge immunization 8 weeks after induction of unresponsiveness, and they were fully responsive to challenge immunization at 12 weeks. Animals given a single dose of 0.1, 0.4, or 1.6 microgram of polysaccharide produced a marked anamnestic response after challenge immunization. Repeated injections of subimmunogenic doses of polysaccharide did not produce a marked anamnestic response and would induce unresponsiveness only when the cumulative dose reached 100 to 400 microgram of polysaccharide, suggesting that injected cryptococcal polysaccharide might be sequestered in some manner until an amount of antigen sufficient for induction of unresponsiveness is accumulated. This possibility was confirmed by immunofluorescence studies that revealed a long-term deposition of polysaccharide in the tubular epithelial cells of the kidney.