title: The roles of IL-2 and IL-10 enhance anti-CD45RBmAb immune inhibition in allograft skin.
abstract: As a new type of immune tolerance inducer, anti-CD45RB monoclonal antibodies (anti-CD45RBmAb) can prolong the graft survival time of animal organs or cell transplantation as well as induce stable immune tolerance. Both interleukin (IL)-2 and IL-10 have important roles in the induction and maintenance of immunological tolerance. However, whether these cytokines combined with anti-CD45RBmAb can promote immune tolerance is poorly understood. Therefore, we investigated the effect of IL-2 and IL-10 in vitro and in vivo on the tolerance induction by anti-CD45RBmAb. The changes of Treg and Th17 cells and Th1/Th2 cytokines in anti-CD45RBmAb induced prolongation of skin allograft survival in mice. The finding of a role for IL-2 is novel, of interest, IL-2 promoted anti-CD45RBmAb-induced CD4(+) T cell differentiation into Treg and Th2 cells and suppressed Th17 and Th1 cells. IL-2 enhanced the induction of immune tolerance by anti-CD45RBmAb and significantly prolonged skin graft survival time in vivo. In contrast, this effect should be demonstrated experimentally by neutralizing IL-2 and inhibition of the effect of anti-CD45RBmAb, and neutralizing IL-10 showed no effect for anti-CD45RBmAb-induced tolerance. These data reveal that IL-2 significantly enhances anti-CD45RBmAb-induced immune tolerance via up-regulated T regulatory (Treg) cells and the balance of Th1/Th2 shifts. Conversely, IL-10 showed no effect on anti-CD45RBmAb-induced tolerance.
authors.affiliation: The Key Laboratory of Stem Cell and Cellular Therapy, the Second Clinical Medical College (Shenzhen People's Hospital), Ji'nan University, Nu.1017, North Road of Eastern Gate, Shenzhen, 518020, China.
authors.forename: Wei-Jian
authors.initials: WJ
authors.lastname: Guo
authors.forename: Hui
authors.initials: H
authors.lastname: Qi
authors.forename: Chun-Yan
authors.initials: CY
authors.lastname: Deng
authors.forename: Han-Xin
authors.initials: HX
authors.lastname: Zhou
authors.forename: Shao-Ping
authors.initials: SP
authors.lastname: Deng
authors.forename: Fu-Rong
authors.initials: FR
authors.lastname: Li
mesh_terms: D064591:Allografts / Q000276:immunology; D000818:Animals; D019138:Antibodies, Blocking / Q000008:administration & dosage; D000911:Antibodies, Monoclonal / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D006085:Graft Survival / Q000187:drug effects; D007108:Immune Tolerance / Q000187:drug effects; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism*; D007376:Interleukin-2 / Q000276:immunology / Q000378:metabolism*; D017493:Leukocyte Common Antigens / Q000276:immunology; D016131:Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016038:Skin Transplantation; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology*; D058408:Th1-Th2 Balance / Q000187:drug effects; D023001:Transplantation Tolerance / Q000187:drug effects
chemical_list: D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D016207:Cytokines; D007376:Interleukin-2; D016753:Interleukin-10; D017493:Leukocyte Common Antigens