T cell-dependent immune response in C1q-deficient mice: defective interferon gamma production by antigen-specific T cells.
The role of the classical complement pathway in humoral immune responses was investigated in gene-targeted C1q-deficient mice (C1qA-/-). Production of antigen-specific immunoglobulin (Ig)G2a and IgG3 in primary and secondary responses to T cell-dependent antigen was significantly reduced, whereas IgM, IgG1, and IgG2b responses were similar in control and C1qA-/- mice. Despite abnormal humoral responses, B cells from C1qA-/- mice proliferated normally to a number of stimuli in vitro. Immune complex localization to follicular dendritic cells within splenic follicles was lacking in C1qA-/- mice. The precursor frequency of antigen-specific T cells was similar in C1qA-/- and wild-type mice. However, analysis of cytokine production by primed T cells in response to keyhole limpet hemocyanin revealed a significant reduction in interferon-gamma production in C1qA-/- mice compared with control mice, whereas interleukin 4 secretion was equivalent. These data suggest that the classical pathway of complement may influence the cytokine profile of antigen-specific T lymphocytes and the subsequent immune response.
Cutler
A J
AJ
Rheumatology Section, Division of Medicine, Imperial College School of Medicine, Hammersmith Hospital, London W12 ONN, United Kingdom.
Botto
M
M
van Essen
D
D
Rivi
R
R
Davies
K A
KA
Gray
D
D
Walport
M J
MJ
D000818:Animals; D000906:Antibodies / Q000276:immunology; D000936:Antigen-Antibody Complex / Q000276:immunology; D000941:Antigens / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D002455:Cell Division; D015922:Complement C1q / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D003171:Complement Pathway, Classical; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000276:immunology*
D000906:Antibodies; D000936:Antigen-Antibody Complex; D000941:Antigens; D015847:Interleukin-4; D015922:Complement C1q; D007371:Interferon-gamma