Interleukin 10 inhibits T cell alloreaction induced by human dendritic cells.
Human dendritic cells (DC) generated from CD34+ hematopoietic progenitors cultured in the presence of granulocyte macrophage colony stimulating factor (GM-CSF) and tumor necrosis factor (TNF)-alpha are related to Langerhans cells (DLC) and have been shown to 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 of both CD4+ and CD8+ T cells induced by allogeneic CD1a+ DLC. The alloreaction induced by DLC generated after 5-18 days of culture of CD34+ HPC was equally inhibited by h-IL-10, thus indicating that DLC were sensitive to h-IL-10 at all stages of differentiation. This is further indicated by the h-IL-10-induced inhibition of the T cell alloreaction mediated by interdigitating DC freshly isolated from tonsils. h-IL-10 specifically acted on DLC as it did not affect the proliferation induced by Epstein-Barr virus lymphoblastoid cell lines (EBV-LCL) nor that induced by immobilized anti-CD3. The inhibitory effect of h-IL-10 was not due to the production of suppressive factors by the DLC, as the addition of 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-gamma) observed after 24 h of co-culture may explain the inhibition of T cell DNA synthesis detected 3 days later. The h-IL-10-induced inhibition of human DC mediated alloreaction advocates considering the use of h-IL-10 in the prevention of transplant rejection and graft versus host disease, phenomena initiated by DC.
Caux
C
C
Schering-Plough, Laboratory for Immunological Research, Dardilly, France.
Massacrier
C
C
Vanbervliet
B
B
Barthelemy
C
C
Liu
Y J
YJ
Banchereau
J
J
D017951:Antigen Presentation / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology; D018949:Antigens, CD1; D018952:Antigens, CD34; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology*; D005312:Fetal Blood / Q000166:cytology; D005434:Flow Cytometry; D006801:Humans; D016753:Interleukin-10 / Q000502:physiology*; D007519:Isoantigens / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D014066:Palatine Tonsil / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology*
D015703:Antigens, CD; D018949:Antigens, CD1; D018952:Antigens, CD34; D016207:Cytokines; D007519:Isoantigens; D016753:Interleukin-10