AN IMMUNOREGULATORY ROLE FOR NEUTROPHILS IN CD4(-HELPER SUBSET-SELECTION IN MICE WITH CANDIDIASIS() T)

Granulocytes may serve immunoregulatory and effector roles in differen t limbs of the immune response to infection. Using live vaccine strain or virulent challenge in mucosal or systemic infection of mice with C andida albicans, we examined the effect of mAb-mediated depletion of n eutrophils on the course of primary and secondary challenge and on dev elopment of CD4(+) cell-dependent immunity. We obtained evidence of de leterious effects of neutrophil depletion occurring at the time of inf ection under all conditions of testing, both in naive and in previousl y immunized mice. In contrast, neutrophil depletion appeared to benefi t the hosts late in the course of an overwhelming systemic infection. In an attempt to correlate neutrophil function with the nature of the T cell response, we tested the ability of neutrophils to produce cytok ines associated with functionally distinct CD4(+) Th cell responses to Candida. We found that neutrophils were endowed with the capacity to secrete IL-12 and IL-10 in vitro in response to the yeast. Neutrophil ablation early in the course of Th1-associated, self-limiting infectio n appeared to change the qualitative development of the T cell respons e, and rendered mice susceptible to infection. In addition to long rec ognized contributions to acute anti-candidal responses, these data sug gest an important role for neutrophils both in initiation and in expre ssion of Candida-specific immunity.