Cutting edge: allogeneic CD4+CD25+Foxp3+ T regulatory cells suppress autoimmunity while establishing transplantation tolerance.
An important unresolved question with regard to T regulatory (Treg) cell specificity and suppressive activity is whether allogeneic Treg cells inhibit self-reactive T cells. In the present study, this issue was addressed using IL-2Rbeta-deficient mice that develop rapid lethal autoimmunity due to impaired production of Treg cells. We show that adoptive transfer of completely MHC-mismatched Treg cells into IL-2Rbeta(-/-) mice resulted in life-long engraftment of the donor cells, which exhibited skewed reactivity toward host alloantigens, and prevented autoimmunity. Thus, Treg cells that underwent thymic selection by peptide/MHC class II complexes distinct from those recognized by autoreactive T cells, still effectively suppress autoimmunity. Remarkably, when such animals were skin grafted, they exhibited dominant tolerance to those grafts bearing MHC molecules that were shared with donor Treg cells. Collectively, these data demonstrate that effective engraftment by allogeneic Treg cells controls autoimmunity and results in permissive conditions for long-term acceptance of allografts.
Adeegbe
Dennis
D
Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, FL 33101, USA.
Bayer
Allison L
AL
Levy
Robert B
RB
Malek
Thomas R
TR
D019264:Adoptive Transfer; D000744:Anemia, Hemolytic, Autoimmune / Q000235:genetics / Q000276:immunology / Q000517:prevention & control; D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology / Q000517:prevention & control*; D051858:Forkhead Transcription Factors / Q000096:biosynthesis*; D053646:Interleukin-2 Receptor beta Subunit; D007519:Isoantigens / Q000096:biosynthesis / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics; D016038:Skin Transplantation / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation*; D023001:Transplantation Tolerance / Q000235:genetics / Q000276:immunology*; D014184:Transplantation, Homologous
D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; C508022:Il2rb protein, mouse; D053646:Interleukin-2 Receptor beta Subunit; D007519:Isoantigens; D015375:Receptors, Interleukin-2