T cell-dependent immune response in C1q-deficient mice: defective interferon ? 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 (lg)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-? 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.