Chronic infection and reactivation in a pulmonary challenge model of histoplasmosis

Reactivation may be a mechanism for the development of histoplasmosis in AI DS. In this study, histoplasmosis was reactivated by the depletion of CD4 a nd CD8 lymphocytes in mice. CD4 and/or CD8 depletion beginning 1 month afte r intratracheal infection and continuing for 2 months caused reactivation w ith a 2.1 log/g increase in the lungs and a 1.5 log increase in the spleen of B6C3F1 mice. Because control animals showed persistent infection, a subs equent experiment sought to determine the long-term outcome in competent mi ce. Twelve of 32 immunocompetent mice died at weeks 26-52 of infection, and 4 survivors appeared to be clinically ill; all ill mice had high fungus bu rdens, whereas cultures were sterile in the healthy mice. Eight of the surv iving healthy-appearing mice underwent autopsy 2 years after infection, and cultures were sterile. Thus, 16 of 32 immunocompetent mice exhibited progr essive infection. CD4 and/or CD8 depletion exacerbated infection, but a chr onic progressive and ultimately fatal infection occurred in half the immuno competent mice.