CD4+ T cell-dependent acquired state of immunity that protects the brain against Cryptococcus neoformans

In immunodeficient hosts, a failure in defense mechanisms allows Cryptococcus neoformans to establish foci of infection in the brain. Immune and nonspecific responses in the primary site of infection in the lung have been described, but those extrapulmonary defense mechanisms that can be mobilized against the yeast have received little attention. This paper describes a response expressed against yeast in the brain of immunocompetent hosts, a response that is weakened in hosts deficient in CD4+ T cells. When a small number of yeast gain access to the vasculature, for example through an i.v. injection, about 0.1% establish themselves in the brain. Normal mice but not SCID mice have the capacity to suppress the multiplication of these yeast cells. The host response is accelerated in mice that are recovering from a primary lung infection, resulting in long term survival without antibiotic chemotherapy. This response is ablated by anti-CD4 mAb treatment and CD4+ cells obtained from infected primed donors are needed to confer immunity on SCID recipients. The critical target for the anti-Cryptococcus immune response are yeast in the brain cortex. However, rather than preventing the colonization of the brain by blood-borne yeast, immunity apparently serves to restrict the growth of yeast in a small number of established foci.