Required early complement activation in contact sensitivity with generation of local C5-dependent chemotactic activity, and late T cell interferon γ: A possible initiating role of B cells

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Abstract

Complement (C) is an important component of innate immunity, and was also shown recently to participate in induction of acquired B cell humoral immunity. In this study, we present evidence that C also participates in acquired T cell immunity. We found that C was involved in early events of the efferent elicitation phase of contact sensitivity (CS), and delayed-type hypersensitivity (DTH). Thus, CS and DTH were inhibited by administration of a C-blocker, soluble recombinant C receptor-1 (sCR1), when given 30 min before, but not 3 h after local antigen challenge. Among C components, local C5 were thought crucial to elicitation of CS, since local administration of anti-C5 monoclonal antibodies or locally injected C-depleting cobra venom factor also inhibited CS and DTH. These findings were consistent with our previous finding of the importance of C5 for CS elicitation, using congenitally C5-deficient mice. To dissect the mechanism of C dependence in CS, we demonstrated that locally increased early macrophage chemotactic activity (probably C5a) in evolving CS skin extracts, as well as late elaboration of IFN-γ were both inhibited by anti-C treatment. In addition, histological analysis showed that leukocyte recruitment into CS ear sites was similarly C-dependent. Furthermore, an initiating role or B cell-derived C- fixing immunoglobulin was suggested by demonstration of impaired CS responses in B cell-deficient mice. In summary, these results suggest that C was activated locally, perhaps via a B cell product, in an important early component of the stepwise events necessary to elicit CS, leading to local production of C5-dependent macrophage chemotactic activity and later IFN-γ, and subsequently leading to cell infiltration, for development oft cell- dependent CS.

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Tsuji, R. F., Geba, G. P., Wang, Y., Kawamoto, K., Matis, L. A., & Askenase, P. W. (1997). Required early complement activation in contact sensitivity with generation of local C5-dependent chemotactic activity, and late T cell interferon γ: A possible initiating role of B cells. Journal of Experimental Medicine, 186(7), 1015–1026. https://doi.org/10.1084/jem.186.7.1015

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