IL-12 is produced by antigen-presenting cells stimulated with soluble alphabeta TCR and restores impaired T(h)1 responses.
Contact sensitivity (CS) is a cutaneous T(h)1 response that is induced by skin painting with reactive hapten. In prior in vivo studies of CS, we showed that recombinant soluble alphabetaTCR (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-gamma production by the CS-effector cells. Importantly, addition of two different sTCR, of unrelated specificity, reversed this down-regulation and thus restored IFN-gamma 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-gamma production from the T(h)1 CS-effector cells.
Kawamoto
K
K
Department of Veterinary Surgery, College of Agriculture, University of Osaka Prefecture, Sakai, Osaka 593, Japan.
Paliwal
V
V
Ramabhadran
R
R
Szczepanik
M
M
Tsuji
R F
RF
Matsuda
H
H
Askenase
P W
PW
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D003877:Dermatitis, Contact / Q000209:etiology / Q000276:immunology*; D006241:Haptens / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism*; D018664:Interleukin-12 / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000276:immunology; D051379:Mice; D008808:Mice, Inbred CBA; D010853:Picryl Chloride / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology; D012995:Solubility; D013154:Spleen / Q000166:cytology / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*
D006241:Haptens; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011994:Recombinant Proteins; D018664:Interleukin-12; D007371:Interferon-gamma; D010853:Picryl Chloride