The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1997/10/1015/ $5.00
The Journal of Experimental Medicine, Volume 186, Number 7, October 6, 1997 1015-1026

Articles

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

Ryohei F. Tsuji*, Gregory P. Geba{ddagger}, Yi Wang§, Keiko Kawamoto||, Louis A. Matis§, and Philip W. Askenase

From the * Noda Institute for Scientific Research, Noda-shi, Chiba-ken 278, Japan; {ddagger} Section of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520-8013; § Alexion Pharmaceuticals Inc., New Haven, Connecticut 06511; || Department of Veterinary Surgery, College of Agriculture, Osaka Prefecture University, Sakai, Osaka 593, Japan; and the Section of Allergy and Clinical Immunology, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520-0813

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.

Address correspondence to Dr. Ryohei F. Tsuji, Noda Institute for Scientific Research, 399 Noda, Noda-shi, Chiba-ken 278, Japan. Phone: 81-471-23-5573; FAX: 81-471-23-5550.

The authors are indebted to Dr. Lindsay N. Donald of T Cell Sciences, Inc. for the kind gift of sCR1. We thank Drs. Peter J. Lachmann, Tony Hugli, Vipin Paliwal, and Rajani Ramabhadran for their valuable advice. We are also grateful to Marilyn Avallone for her superb secretarial skills.

1 Abbreviations used in this paper: CS, contact sensitivity; CVF, cobra venom factor; DTH, delayed-type hypersensitivity; PCl, picryl chloride (TNP-chloride); sCR1, soluble complement receptor type 1; ZAMS, zymosan activated mouse serum; 5-HT, serotonin (5-hydroxy-tryptamine).


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