In Vitro Assays of Cellular Immunity in Progressive Coccidioidomycosis: Evaluation of Suppression with Parasitic-phase Antigen

Patients with progressive coccidioidomycosis commonly have depressed cell-mediated immune responses to coccidioidal antigens. We studied in vitro lymphocyte transformation in response to spherulin, as extract of the parasitic phase of Coccidioides immitis, and the nonspecific mitogen phytohemagglutinin in patients with progressive disseminated coccidioidomycosis who were anergic to spherulin and in healthy skin test-positive and skin test-negative control subjects. Lymphocyte responses to phytohemagglutinin were indistinguishable for all three groups. When assayed in pooled blood group AB serum, lymphocyte responses to spherulin were identical for patients and skin test-positive control subjects; however, the patients' responses to spherulin were depressed in autologous serum. Prolonged incubation of cells in vitro did not restore the hyporesponsiveness. Serial studies of the patients revealed a trend toward restoration of the lymphocyte response during therapy. Preliminary experiments suggest that, although there were no intrinsic cell defects in these patients with coccidioidomycosis, there may be specificity of patient cells to be suppressed by serum. A prospective study of the incidence of depression of lymphocyte responsiveness in autologous serum revealed that this occurs in a minority of patients with negative spherulin skin tests, is rare in patients with positive skin tests, and appears to be associated with clinical deterioration.