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Significance There is increasing evidence that CD8+ regulatory T cells (CD8 Treg) can modulate the immune response in the context of autoimmune disease, infection, and cancer. Here we asked whether this regulatory mechanism might control the host response to transplanted heart allografts. We report that CD8 Treg that recognize Qa-1, the murine homolog of HLA-E, strongly inhibits host production of antibodies specific for the donor organ. Since the production of antidonor antibodies is currently a major barrier to successful transplantation, identification of this Qa-1/HLA-E-dependent pathway may pave the way to approaches to this pressing clinical problem.

Regulatory CD8 T cells that recognize Qa-1 expressed by CD4 T-helper cells inhibit rejection of heart allografts