Effects of exogenous interleukin-10 in a murine model of graft-versus-host disease to minor histocompatibility antigens.
IL-10 is a regulatory cytokine of both T cells and monocytes. We have investigated the ability of IL-10 to regulate responses to alloantigens in vitro and in vivo. Addition of IL-10 to mixed lymphocyte cultures profoundly decreased the proliferation and IL-2 production by donor B10.BR cells stimulated with CBA cells expressing minor histocompatibility antigens. Administration of IL-10 for a period of 2 weeks after bone marrow transplantation decreased the expansion of CD4+ and CD8+ donor T cells. In addition, splenocytes from BMT mice treated with IL-10 secreted less IFN-gamma after stimulation with Con A in vitro. The suppression of the mitogen-driven proliferative response of lymphocytes from the IL-10-treated group could also be reversed with significantly less anti-IFN-gamma antibody than for saline-treated controls. However, treatment with IL-10 was not sufficient to alter significantly the clinical course of graft-versus-host disease in CBA recipient mice as assessed by survival, weight loss, and splenomegaly. The results suggest that exogenous IL-10 suppresses the afferent Th1 response in a graft-versus-host reaction but does not significantly diminish the effector stage of graft-versus-host disease.
Krenger
W
W
Department of Pediatric Oncology, Dana Farber Cancer Institute, Boston, Massachusetts 02115.
Snyder
K
K
Smith
S
S
Ferrara
J L
JL
D000818:Animals; D000954:Antigens, Surface / Q000235:genetics; D001835:Body Weight; D016026:Bone Marrow Transplantation / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D006086:Graft vs Host Disease / Q000235:genetics / Q000276:immunology* / Q000401:mortality; D007108:Immune Tolerance; D016753:Interleukin-10 / Q000097:blood / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D015778:Minor Histocompatibility Antigens / Q000276:immunology*; D010641:Phenotype; D013154:Spleen / Q000473:pathology; D013163:Splenomegaly / Q000276:immunology; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology
D000954:Antigens, Surface; D015778:Minor Histocompatibility Antigens; D016753:Interleukin-10