Journal
JOURNAL OF IMMUNOLOGY
Volume 176, Issue 12, Pages 7149-7153Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.176.12.7149
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Funding
- NCI NIH HHS [R01 CA45957] Funding Source: Medline
- NIAID NIH HHS [R01 AI55815, R01 AI46689] Funding Source: Medline
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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-2R beta-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-2R beta(-/-) 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 antoimmunity. 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.
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