Effect of in vitroexpanded CD4(+)CD25(+)Foxp3(+) regulatory T cell therapy combined with lymphodepletion in murine skin allotransplantation.
A promising approach for preventing allograft rejection involves shifting the balance between cytopathic and regulatory T cells to dominance of the latter cell type. Nonspecific lymphodepletion was conducted by administration of depleting anti-CD4 and anti-CD8 antibodies to reduce effector T cells and adoptive transfer of ex vivo-expanded host Treg cells by stimulation with donor dendritic cells to augment the Treg cell compartment. Evaluation of an MHC-mismatched skin allograft model revealed that combined therapy with these two protocols consistently induced modest prolongation of allograft survival, although all skin grafts were eventually rejected. The administration of IL-2/anti-IL-2 complexes significantly improved the efficacy of combination therapy via promoting the expansion of adoptively transferred Treg cells as well as endogenous recipient Treg cells. We conclude that Treg cell therapy combined with lymphodepletion is of practical benefit for the control of allograft rejection, but requires supplementary measures to promote immune tolerance.
Park
Youn-Hee
YH
Asan Institute for Life Sciences, Ulsan University College of Medicine, Seoul 138-736, Korea.
Koo
Sun-Kyung
SK
Kim
Youngji
Y
Kim
Hye-Mi
HM
Joe
In-Yi
IY
Park
Chan-Sik
CS
Kim
Song-Cheol
SC
Han
Duck-Jong
DJ
Lim
Dong-Gyun
DG
D019264:Adoptive Transfer / Q000379:methods*; D000818:Animals; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D051858:Forkhead Transcription Factors / Q000276:immunology; D006085:Graft Survival / Q000276:immunology*; D006651:Histocytochemistry; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D053208:Kaplan-Meier Estimate; D007959:Lymphocyte Culture Test, Mixed; D008212:Lymphocyte Depletion / Q000379:methods*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D016038:Skin Transplantation / Q000276:immunology / Q000379:methods*; D013047:Specific Pathogen-Free Organisms; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit