Experimental induction of anergy to coccidioidin by antigens of Coccidioides immitis.

Failure to react to coccidioidin (anergy) often occurs in patients with disseminated coccidioidomycosis. One possible reason may be desensitization by excessive amounts of antigen. This was studied experimentally by injection of soluble and hyphal antigens of Coccidioides immitis into coccidioidin- and tuberculin-sensitive guinea pigs. Guinea pigs sensitized by injection of killed hyphal cells of C. immitis in complete Freund adjuvant were subsequently injected daily either with soluble coccidioidal antigen administered intraperitoneally or with hyphal antigen administered either subcutaneously or intraperitoneally. Gradual loss of cutaneous reactivity to coccidioidin occurred, but the reactivity to tuberculin remained unimpaired. The rapidity of desensitization was roughly proportional to the dose of antigen with desensitization occurring as early as 6 days after beginning injections. This anergic state was temporary, and reactivity returned several days after discontinuing injection of antigen. Injection of coccidioidal antigen led to production of coccidioidal complement-fixing antibody, but there was no consistent relationship between the antibody titer and state of cutaneous reactivity to coccidioidin. Peritoneal exudate or pulmonary alveolar cells from desensitized animals migrated freely in the presence of coccidioidin but were inhibited in the presence of tuberculin. Heat treatment did not impair the capacity of the soluble or hyphal antigen to induce anergy, thus suggesting that the antigen active in complement fixation was perhaps not involved in desensitization. Polysaccharide obtained by ethanol precipitation of dialyzed coccidioidin failed to induce anergy. Dialysis of the soluble coccidioidal antigen caused the loss of the desensitizing activity. Thus, specific desensitization could be induced by administration of large doses of coccidioidal antigen but dialyzable components appear important in this desensitization.