Human regulatory T cells and autoimmunity

Abstract

CD4+CD25+ regulatory T cells (Treg) appear to be critical in regulating immune responses to self-antigens. Treg deficiency is associated with several human autoimmune diseases. Although substantial progress has been made in the study of murine and human Treg, their fundamental mechanism of action remains unknown. In this review, we discuss the phenotype of human natural Treg, their functional mechanism, and their role in autoimmune disease.

Figure 1

CD4⁺CD25^high cells isolated from patients with MS suppress less efficiently than Tregs purified from healthy donors. CD4⁺CD25⁻ responder T cells and CD4+CD25high cells from six MS patients and six normal controls were stimulated with soluble anti-CD3 and anti-CD28 (5μg/ml) alone or cocultured at different responder/suppressor rations (1:1, 1:1/2, and 1:1/4). The average proliferative response was 13,494 cpm in the patient group and 15,974 cpm in the control group. The percent inhibition of coculture proliferation was calculated in patients with MS (open sircles) and healthy controls (closed squares). (Reprint permission from J. Exp. Med.)

Figure 2

HLA-DR⁺ Tregs and HLA-DR⁻ Tregs have distinct mechanisms of suppression. HLA-DR⁺ Tregs directly inhibit both proliferation and cytokine suppression through a cell-contact dependent mechanism, while HLA-DR⁻ Tregs induce secretion of IL-4 and IL-10 in Tresp before suppressing proliferation.