T helper cell dichotomy to Candida albicans: implications for pathology, therapy, and vaccine design.

Acquired immunity to Candida albicans is believed to prevent mucosal colonization of adult immunocompetent individuals from progressing to symptomatic infection. Resistance to disease appears to correlate with the detection of delayed-type hypersensitivity responses in vivo and a T helper type 1 (Th1) cytokine secretion profile in vitro. Cellular immunodeficiency, particularly HIV infection, greatly increases the risk of mucosal infection, confirming that CD(4+)-cell-directed immunity is effective locally in controlling infectivity of the yeast. While Th1-type CD4+ cell activation resulting in phagocyte-dependent immunity clearly represents an important mechanism of anticandidal resistance, clinical observations suggest that Th2-type CD4+ cell reactivity may be triggered by Candida antigens in several disease states, including symptomatic infections and immunopathology. This may imply that a Th1-type pattern of reactivity characterizes the saprophytic yeast carriage and resistance to disease by healthy humans, whereas Th2-type responses would be mostly associated with pathology. Moreover, Candida-specific T helper responses, namely humoral and cell-mediated immunity, appear to be reciprocally regulated, as typically occurs in experimental models of parasitic and retroviral infection, where the Th1/Th2 paradigm of acquired immunity has been best characterized. Recent studies, besides providing direct evidence for the occurrence of cross-regulatory Th1 and Th2 responses in mice with candidiasis, emphasize the potential of cytokine/anticytokine therapy for recruiting Candida-specific responses toward protective, Th1-type CD4+ cell reactivity. At the same time, these studies call attention to the possible consequences of C. albicans infection for immunopathology, allergy, and coinfection.