The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1998/6/1789/ $5.00
The Journal of Experimental Medicine, Volume 187, Number 11, June 1, 1998 1789-1797


Articles

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

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

From the * Rheumatology Section and {ddagger} 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-{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.

Key Words: complement • deficiency • immune response • interferon {gamma} • gene targeting


Address correspondence to Mark J. Walport, Division of Medicine, Rheumatology Section, Imperial College School of Medicine, Hammersmith Hospital, Du Cane Rd., London W12 ONN, UK. Phone: 0044-181-383-3299; Fax: 0044-181-743-3109; E-mail: mwalport{at}rpms.ac.uk

Abbreviations used: FDC, follicular dendritic cell; GCDC, dendritic cell identified within murine germinal center; HAGG, heat-aggregated human {gamma}-globulin; IDC, interdigitating dendritic cell; PNA, peanut agglutinin; TD, T cell–dependent.


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