Fc Receptor–Mediated Antibody Regulation of T Cell Immunity against Intracellular Pathogens

Immunity to intracellular microbial pathogens, including Chlamydia species, is controlled primarily by cell-mediated effector mechanisms, yet, the absence of antibodies results in inefficient microbial clearance. We investigated the hypothesis that certain Fc receptor functions promote the rapid induction of elevated T helper type 1 (Th1) response, which effectively clears chlamydiae. FcR -/- mice exhibited a delayed and reduced frequency of Chlamydia-specific Thl cells, compared to FcR +/+ mice. In vitro, antichlamydial antibodies increased the rate of Th1 activation by FcR +/+ but not FcR -/- antigen-presenting cells. FcR -/- dendritic cells and the T cell-associated IgG2A and IgA mediate enhanced Thl activation by antibodies. Immunization with chlamydia-antibody complexes induced elevated and protective Thl response. These results provide a mechanistic basis for requiring both T cell and humoral immune responses in protective immunity and vaccine evaluation. Findings offer a paradigm in host defense wherein different effector components function indirectly to maximize the principal effector mechanism.