OPTIMAL CONTROL OF INTERFERON-?? AND TUMOR NECROSIS FACTOR-?? BY INTERLEUKIN-10 PRODUCED IN RESPONSE TO ONE HLA-DR MISMATCH DURING THE PRIMARY MIXED LYMPHOCYTE REACTION1

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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)-γ and tumor necrosis factor (TNF)-α, 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-α and IFN-γ. Using a highly sensitive ELISA, a significant (PP=0.02) and, to a lesser extent, TNF-α(147±56% vs. 112±20%, NS) in 1 compared with 2 DR MM pairs. We conclude that the 1 DR MM setting is associated with optimal IL-10 secretion and more efficient inhibition of IFN-γ and TNF-α compared with the 2 DR MM configuration. Although promoting enhanced IFN-γ and TNF-α release, introduction of an additional DR MM does not result in increased IL-10 production. These data indicating that the IL-10 regulatory feedback loop is more effective in 1 DR rather than complete DR incompatibility could have an impact on matching policies for planned transfusion.

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