Studies on experimental murine histoplasmosis: host protection and cellular immunity

Abstract

Mice immunized subcutaneously with 10⁶ viable yeast cells of Histoplasma capsulatum exhibited host protection to a challenge infection and also exhibited concomitant manifestations of cellular immunity to a culture filtrate antigen (yeast extract dialysate (YED)-histoplasmin). Protective immunity was determined by quantitative culture of organisms from infected spleens on a solid medium containing a growth factor produced by the organism. As early as 4 days following immunization, host protection was observed in mice. Positive footpad swelling, indicative of delayed-type hypersensitivity, also was apparent at the early time period (4–7 days) after immunization. By days 14 and 21 following immunization, the mice exhibited maximum footpad responses and maximum splenic clearance of yeast cells. As an additional correlate of cellular immunity, YED-histoplasmin was coupled with chromic chloride to murine erythrocytes (M-RBC) and mixed with immune or nonimmune splenic lymphocytes to detect antigen-specific rosette forming cells (RFC's). Only splenic lymphocytes from mice immunized with H. capsulatum formed antigen-specific RFC's (≥ 0.2%). Pretreatment of splenic lymphocytes with antitheta (θ) serum plus complement greatly reduced the numbers of RFC's, illustrating their T cell nature. Host protection and cell-mediated immune responses decreased substantially by day 28 following immunization.