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

Terri Moore, Charles O. Ekworomadu, Francis O. Eko, LuCinda MacMillan, Kiantra Ramey, Godwin A. Ananaba, John W. Patrickson, Periakaruppan R. Nagappan, Deborah Lyn, Carolyn M. Black and Joseph U. Igietseme
The Journal of Infectious Diseases
Vol. 188, No. 4 (Aug. 15, 2003), pp. 617-624
Published by: Oxford University Press
Stable URL: http://www.jstor.org/stable/30075688
Page Count: 8
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Fc Receptor-Mediated Antibody Regulation of T Cell Immunity against Intracellular Pathogens
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Abstract

Immunity to intracellular microbial pathogens, including Chlamydia species, is controlled primarily by cellmediated 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.

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