J. Exp. Med., Volume 187, Number 11, June 1, 1998 1789-1797

T Cell-dependent Immune Response in C1q-deficient Mice: Defective Interferon  Production by Antigen-specific T Cells

By Antony J. Cutler,^* Marina Botto,^* Dominic van Essen, Roberta Rivi,^§ Kevin A. Davies,^* David Gray, and Mark J. Walport^*

From the ^* Rheumatology Section and  Immunology Department, Division of Medicine, Imperial College School of Medicine, Hammersmith Hospital, London W12 ONN, United Kingdom; and the ^§ Department of Human Genetics, Sloan Kettering Institute, New York 10021

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- 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.

complement;  deficiency;  immune response;  interferon ;  gene targeting

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