Required early complement activation in contact sensitivity with generation of local C5-dependent chemotactic activity, and late T cell interferon gamma: a possible initiating role of B cells.
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-gamma, 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-gamma, and subsequently leading to cell infiltration, for development of T cell-dependent CS.
Tsuji
R F
RF
Noda Institute for Scientific Research, Noda-shi, Chiba-ken 278, Japan.
Geba
G P
GP
Wang
Y
Y
Kawamoto
K
K
Matis
L A
LA
Askenase
P W
PW
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D002630:Chemotactic Factors / Q000096:biosynthesis; D002633:Chemotaxis; D003167:Complement Activation / Q000276:immunology*; D003182:Complement C5 / Q000276:immunology* / Q000378:metabolism; D003169:Complement Inactivator Proteins / Q000276:immunology / Q000494:pharmacology; D003877:Dermatitis, Contact / Q000276:immunology*; D004546:Elapid Venoms / Q000494:pharmacology; D005260:Female; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D008264:Macrophages / Q000502:physiology; D051379:Mice; D008815:Mice, Inbred Strains; D011951:Receptors, Complement / Q000276:immunology; D011994:Recombinant Proteins / Q000494:pharmacology; D012867:Skin / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
D000911:Antibodies, Monoclonal; D002630:Chemotactic Factors; D003182:Complement C5; D003169:Complement Inactivator Proteins; D004546:Elapid Venoms; D011951:Receptors, Complement; D011994:Recombinant Proteins; C016310:cobra venom factor; C082885:soluble complement inhibitor 1; D007371:Interferon-gamma