IL-10 and IL-4 in skin allograft survival induced by T-cell depletion plus deoxyspergualin.
The mechanisms mediating T-cell depletion plus 15-deoxyspergualin (DSG)-induced prolonged allograft survival or tolerance are uncertain. The purpose of this study is to evaluate the role of IL-4 and IL-10 in prolonged allograft survival induced by T-cell depletion plus DSG. MHC mismatched skin allograft transplantation was performed, using wild-type and three separate knockout (i.e., IL-4-/-, Stat6-/-, or IL-1-/ -) mice as recipients. Induction therapy consisted of T-cell depletion and or brief course of DSG. The data demonstrate that monotherapy with T-cell-depleting mAbs or DSG prolonged skin allograft survival, compared to controls, in wild-type Balb/c recipients [median survival time (MST) = 25 and 21 vs. 10 days, p < 0.007]. T-cell depletion plus DSG further augmented skin allograft survival in wild-type animals relative to monotherapy (MST = 35 days vs. 25 and 21 days, p < 0.006 vs. mAbs or DSG only), and was equally effective in IL-4-/- and Stat6-/- recipients. In contrast, combined therapy was no better than monotherapy in IL-10-/- animals (p > 0.05). Furthermore, skin allograft survival after combined therapy was shorter in IL-10-/- versus wild-type recipients (MST 20 and 41 days, respectively, p < 0.001). IL-4-mediated signaling through Stat6 is dispensable for prolonged allograft survival induced by T-cell depletion plus DSG. In contrast, IL-10 appears to be important for prolonged allograft survival induced by combined therapy in this model.
Asiedu
Clement
C
Division of Transplant Immunology, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL 35294-0019, USA. Clement.Asiedu@ccc.uab.edu
Andrades
Patricio
P
Ray
Peter D
PD
George
James F
JF
Thomas
Judith M
JM
D000818:Animals; D006082:Graft Enhancement, Immunologic; D006085:Graft Survival / Q000187:drug effects / Q000276:immunology; D006146:Guanidines / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000494:pharmacology; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D008212:Lymphocyte Depletion; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D050800:STAT6 Transcription Factor / Q000235:genetics / Q000276:immunology; D016038:Skin Transplantation / Q000276:immunology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
D006146:Guanidines; D007166:Immunosuppressive Agents; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D016753:Interleukin-10; D015847:Interleukin-4; C037258:gusperimus