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

• Published in: The Journal of infectious diseases 2003-08, Vol.188 (4), p.617-624
• Main Authors: Moore, Terri, Ekworomadu, Charles O., Eko, Francis O., MacMillan, LuCinda, Ramey, Kiantra, Ananaba, Godwin A., Patrickson, John W., Nagappan, Periakaruppan R., Lyn, Deborah, Black, Carolyn M., Igietseme, Joseph U.
• Format: Article
• Language: English
• Subjects: AFc receptors; Animals; Antibodies; Antibodies, Bacterial - immunology; Antigens; Antigens, Bacterial - immunology; Bacteriology; Biological and medical sciences; Chlamydia; Chlamydia - immunology; Chlamydia Infections - immunology; Dendritic cells; Dendritic Cells - immunology; Female; Fundamental and applied biological sciences. Psychology; Gene Deletion; Genitalia; Genitalia, Female - immunology; Genitalia, Female - microbiology; Immunity; Infections; Lymphocyte Activation - immunology; Mice; Mice, Knockout; Microbiology; Mucous Membrane - immunology; Mucous Membrane - microbiology; Pathogenesis and Host Response; Pathogenicity, virulence, toxins, bacteriocins, pyrogens, host-bacteria relations, miscellaneous strains; Receptors, Fc - genetics; Receptors, Fc - immunology; T lymphocytes; Th1 Cells - immunology; Vaccination
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/377134

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 Th1 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 Th1 activation by antibodies. Immunization with chlamydia-antibody complexes induced elevated and protective Th1 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