Studies on experimental murine histoplasmosis: host protection and cellular immunity.

Abstract

Mice immunized subcutaneously with 10(6) 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 (greater than or equal to 0.2%). Pretreatment of splenic lymphocytes with antitheta (theta) 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.