Optimal control of interferon-gamma and tumor necrosis factor-alpha by interleukin-10 produced in response to one HLA-DR mismatch during the primary mixed lymphocyte reaction

Transplantation
M ToungouzE Dupont

Abstract

Interleukin (IL)-10 is an immunosuppressive cytokine potentially involved in the control of the allogeneic response. Several studies failed to detect it in mixed lymphocyte reaction supernatants. However, experiments using IL-10-specific antibodies, revealing its inhibitory action on interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha, provided indirect evidence that endogenous IL-10 was produced. The aim of the present work is to elucidate the role of IL-10 during mixed lymphocyte reaction and to investigate the influence of HLA-DR antigens on its production and on the regulatory loop involving TNF-alpha and IFN-gamma. Using a highly sensitive ELISA, a significant (P < 0.0001) but low IL-10 release could be detected (33.7 +/- 3.6 pg/ml) in response to HLA-DR disparities. However, IL-10 release was not graded as 1 DR mismatch (MM)-induced maximal secretion (32.3 +/- 5.1 pg/ml). This contrasted with TNF-alpha and IFN-gamma productions, which significantly increased in 2 DR MM pairs. Addition to IL-10-specific antibodies resulted in higher enhancement of INF-gamma (235 +/- 38% vs. 122 +/- 39%, P = 0.02) and, to a lesser extent, TNF-alpha (147 +/- 56% vs. 112 +/- 20%, NS) in 1 compared with 2 DR MM pairs. We conclude that...Continue Reading

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Citations

Feb 10, 2000·Springer Seminars in Immunopathology·M R ShurinM T Lotze
Jul 20, 2001·Journal of Virology·C Söderberg-NauclérJ A Nelson
Sep 15, 2000·Blood Reviews·A Brand
Aug 25, 1999·Medical Hypotheses·H H MaesR F Maes

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