T-HELPER CELL DICHOTOMY TO CANDIDA-ALBICANS - IMPLICATIONS FOR PATHOLOGY, THERAPY, AND VACCINE DESIGN

Acquired immunity to Candida albicans is believed to prevent mucosal c olonization of adult immunocompetent individuals from progressing to s ymptomatic 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 i mmunodeficiency, particularly HIV infection, greatly increases the ris k of mucosal infection, confirming that CD4+-cell-directed immunity is effective locally in controlling infectivity of the yeast. While Th1- type CD4+ cell activation resulting in phagocyte-dependent immunity cl early represents an important mechanism of anticandidal resistance, cl inical observations suggest that Th2-type CD4+ cell reactivity may be triggered by Candida antigens in several disease states, including sym ptomatic infections and immunopathology. This may imply that a Th1-typ e pattern of reactivity characterizes the saprophytic yeast carriage a nd 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 mod els of parasitic and retroviral infection, where the Th1/Th2 paradigm of acquired immunity has been best characterized. Recent studies, besi des providing direct evidence for the occurrence of cross-regulatory T h1 and Th2 responses in mice with candidiasis, emphasize the potential of cytokine/anticytokine therapy for recruiting Candida-specific resp onses toward protective, Th1-type CD4+ cell reactivity. At the same ti me, these studies call attention to the possible consequences of C. al bicans infection for immunopathology, allergy, and coinfection.