Interleukin 10 inhibits T cell alloreaction induced by human dendritic cells

Human dendritic cells (DC) generated from CD34⁺ hematopoieticprogenitors cultured in the presence of granulocyte macrophagecolony stimulating factor (GM-CSF) and tumor necrosis factor(TNF)- are related to Langerhans cells (DLC) and have been shownto induce a strong proliferation of allogeneic CD4⁺ T cells.The present study shows that recombinant human IL-10 (h-IL-10)inhibits the primary and secondary proliferative responses ofboth CD4⁺ and CD8⁺ T cells induced by allogenelc CD1a⁺ DLC.The alloreaction induced by DLC generated after 5–18 daysof culture of CD34⁺ HPC was equally inhibited by h-IL-10, thusindicating that DLC were sensitive to h-IL-10 at all stagesof differentiation. This is further indicated by the h-IL-10-inducedinhibition of the T cell alloreaction mediated by interdigitatingDC freshly isolated from tonsils. h-IL-10 specifically actedon DLC as it did not affect the proliferation induced by Epstein-Ban-viruslymphoblastoW cell lines (EBV-LCL) nor that induced by immobilizedanti-CD3. The inhibitory effect of h-IL-10 was not due to theproduction of suppressive factors by the DLC, as the additionof DLC and IL-10 did not inhibit EBV-LCL-induced T cell proliferation.Rather, the inhibition of cytokine production (IL-2, GM-CSF,TNF, IFN-) observed after 24 h of co-culture may explain theinhibition of T cell DNA synthesis detected 3 days later. Theh-IL-10-lnduced inhibition of human DC mediated alloreactionadvocates considering the use of h-IL-10 In the prevention oftransplant refection and graft versus host disease, phenomenainitiated by DC.