Immunoregulatory responses in experimental disseminated histoplasmosis: lymphoid organ histopathology and serological studies.

To study immunoregulatory mechanisms in systemic histoplasmosis, a highly reproducible model of infection was established in C3H/Anf mice. Intravenous inoculation of 6- to 8-week-old mice with from 5 x 10(5) to 10 x 10(5) cells of yeast-phase Histoplasma capsulatum strain G-217B produced disseminated infection that resolved over an 8-week period without therapeutic intervention. Serological studies demonstrated complement-fixing antibody production to yeast- and mycelial-phase antigens of H. capsulatum. Complement-fixing antibody to the former was detected at week 1, and it peaked at week 3 and declined thereafter. Complement-fixing antibody to mycelial-phase antigen(s) appeared later (week 3) and did not peak until week 18. Grossly, the spleens of infected mice were enlarged from three to four times normal size during peak infection, whereas the thymuses were markedly involuted. Conversely, at week 8 the average spleen size was considerably smaller and the thymic mass was increased relative to the mass at week 3. Histopathologically, the paracortical regions of lymph nodes and the white pulp (periarteriolar lymphocyte sheaths) and marginal zones of the spleen were heavily infiltrated by granulomata at week 1. By week 8, the infiltrates in these areas had largely resolved. Thymocytes were severely depleted from the cortical lobules of the thymus at week 1; however, thymic cellularity was restored by week 8. These reciprocal changes in cellularity of the thymus and spleen during active infection may be of importance with reference to the disturbances of immunoregulation that we have observed in Histoplasma-infected mice.