PMID: 8946679Oct 1, 1996Paper

Inhibition of the human allogeneic mixed lymphocyte response by cyclosporin A: relationship with the IL-12 pathway

Tissue Antigens
B BonnotteS Chouaib

Abstract

Interleukin-12 (IL-12) is an important cytokine in the control of cell-mediated immunity. We have previously shown that endogenous IL-12 plays a role in the development of human allogeneic response. In the present study, we investigated the relationship between Cyclosporin A (CsA)-inhibitory effect and IL-12 pathway during human alloreaction in vitro. CsA addition at the sensitizing phase of primary mixed lymphocyte reaction (MLR) resulted in the inhibition of both p40 and p70 IL-12 production in a dose-dependent manner. In contrast, CsA had no effect on IL-12-receptor beta 1 chain (IL-12 R beta 1) expression in T cells induced upon allogeneic activation. Addition of exogenous IL-12 significantly restored CsA-inhibited alloreactive cytotoxic T lymphocyte (CTL) generation and had a marginal effect on T cell proliferative response. The IL-12-induced restoration of CTL generation was IFN gamma-mediated, as it was significantly altered when anti-IFN gamma was added. The restoration of CTL activity by exogenous IL-12 correlated with the capacity of this cytokine to partially restore granzyme B mRNA expression in alloreactive CTL. This study indicates that inhibition of IL-12 production is a novel additional mechanism for the inhibit...Continue Reading

References

Mar 7, 1991·The New England Journal of Medicine·J L Ferrara, H J Deeg
Nov 15, 1995·Transplantation·A NaglerV Barak
Dec 20, 1994·Proceedings of the National Academy of Sciences of the United States of America·S ChouaibF Mami-Chouaib
Jul 1, 1993·Immunology Today·G Trinchieri
Apr 1, 1996·Journal of Leukocyte Biology·G Trinchieri, F Gerosa

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Citations

Dec 24, 1998·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Y YamaguchiM Ogawa
Mar 27, 2001·Transplantation Proceedings·A D'AmbrosioF Quintieri
Dec 22, 1999·Clinical and Experimental Immunology·W KimH Y Kim
Aug 11, 2007·Analytical Sciences : the International Journal of the Japan Society for Analytical Chemistry·Hidenori NagaiShin-Ichi Wakida
Mar 10, 2004·The Journal of Pharmacy and Pharmacology·Koen VandenbroeckPatrick Matthys
Dec 20, 2011·PLoS Neglected Tropical Diseases·Diana N J LockwoodSujai Suneetha

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