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 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.
Moore
Terri
T
Morehouse School of Medicine, Atlanta, Georgia 30333, USA.
Ekworomadu
Charles O
CO
Eko
Francis O
FO
MacMillan
LuCinda
L
Ramey
Kiantra
K
Ananaba
Godwin A
GA
Patrickson
John W
JW
Nagappan
Periakaruppan R
PR
Lyn
Deborah
D
Black
Carolyn M
CM
Igietseme
Joseph U
JU
D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology; D002689:Chlamydia / Q000276:immunology; D002690:Chlamydia Infections / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D017353:Gene Deletion; D005836:Genitalia, Female / Q000276:immunology / Q000382:microbiology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D009092:Mucous Membrane / Q000276:immunology / Q000382:microbiology; D011961:Receptors, Fc / Q000235:genetics / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D011961:Receptors, Fc