International Immunology, Vol. 12, No. 1, 103-112,
January 2000
© 2000 Japanese Society for Immunology
IL-12 is produced by antigen-presenting cells stimulated with soluble 
ß TCR and restores impaired Th1 responses
Department of Veterinary Surgery, College of Agriculture, University of Osaka Prefecture, Sakai, Osaka 593, Japan
1 Section of Allergy and Clinical Immunology, Department of Internal Medicine, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520-8013, USA
2 Department of Immunology, Jagiellonian University College of Medicine, 31–121, Krakow, Poland
3 Noda Institute for Scientific Research, 399 Noda, Noda-shi, Chiba-ken 278, Japan
4 Faculty of Veterinary Clinic, Department of Agriculture, Tokyo University of Agriculture and Technology, 3-8-5 Saiwai-cho, Fuchu, Tokyo 183, Japan
Correspondence to: P. W. Askenase
Contact sensitivity (CS) is a cutaneous Th1 response that is induced by skin painting with reactive hapten. In prior in vivo studies of CS, we showed that recombinant soluble 
ßTCR (sTCR) acted non-specifically to protect CS-effector T cells from suppression, but no molecular mechanism was determined. In the current study, we employed an in vitro system to investigate the mechanism of how sTCR protect CS-effector T cells from suppression. Immune CS-effector cells and appropriate hapten-conjugated antigen-presenting cells (APC) were incubated together with down-regulatory culture supernatant produced by suppressive spleen cells from mice tolerized i.v. with specific hapten, which produced strong inhibition of IFN-
production by the CS-effector cells. Importantly, addition of two different sTCR, of unrelated specificity, reversed this down-regulation and thus restored IFN- production. We found that the APC, and not the CS-effector T cells, were the locus of the sTCR-mediated protection and showed direct binding of sTCR to APC by flow cytometry. Further, addition of anti-IL-12 showed that sTCR protection was due to IL-12 induced by sTCR and released by the APC, and was confirmed by ELISA measurement of IL-12 induced in APC supernatants by sTCR incubation. These results indicated a possible new regulatory loop in which suppression was reversed by IL-12 derived from APC, following direct surface binding of sTCR, and enhanced by IFN- production from the Th1 CS-effector cells.
Keywords: T cell suppression, delayed-type hypersensitivity, contact sensitivity
Transmitting editor: K. Okumura
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