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

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 of 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 of T cell–dependent CS.

IgE-Mediated Mast Cell Activation Induces Langerhans Cell Migration In Vivo

“…Tsuji et al (44) have shown that C5 is required early for the elicitation phase of contact sensitivity and delayed-type hypersensitivity. C5 was required for macrophage chemotactic activity and the late production of IFN-␥.…”

The Vaccinia Virus Complement Control Protein Modulates Adaptive Immune Responses during Infection

“…Furthermore, mammalian complement regulatory proteins have also been shown to limit accumulation of leukocytes at sites of inflammation. For instance, administering soluble complement receptor 1 (sCR1) to mice has been shown to limit T cell-mediated delayed-type hypersensitivity responses in skin by limiting the influx of T cells to the site of antigen challenge (53,54). Recent efforts to better define the antiviral functions of Abs during poxvirus infection have revealed an important role for complement in Ab-mediated protection (2, 3).…”

Peripheral B-cell CD5 expansion and CD81 overexpression and their association with disease severity and autoimmune markers in chronic hepatitis C virus infection

“…CD5 + B cells are rare in adults, but they are the predominant B cell population in the fetus, in which they appear to constitute a rather primitive but effective first line of defence against foreign antigens [23]. These cells are characterized by the production of low-affinity immunoglobulin M (IgM) with RF activity, arise early in ontogeny and are considered to represent the bridge linking the innate and acquired immune responses [24]. The production of circulating autoantibodies coupled with their increased frequency in rheumatoid arthritis and Sjögren's syndrome has implicated them in the development of autoimmune diseases [25,26].…”