Effect of CD4+CD25+ regulatory T-cells on CD8 T-cell function in patients with autoimmune hepatitis

Background and aims: CD4 T lymphocytes constitutively expressing the IL-2-receptor alpha-chain (CD25) (T-regs) are central to self-tolerance maintenance, preventing the proliferation and effector function of autoreactive T-cells. In autoimmune hepatitis T-regs are defective in number but maintain the ability to suppress IFN gamma production by CD4+CD25- T-cells. We have studied the ability of CD4 + CD25 + (T-regs) to regulate proliferation and cytokine production by CD8 T-cells in patients with autoimmune hepatitis at diagnosis and during remission. Methods: Twenty-five patients were studied. T-regs were purified from PBMCs by CD4 negative selection followed by CD25 positive selection, using immunomagnetic beads. The ability of T-regs to suppress CD8 T-cell proliferation was assessed by H-3-thymidine incorporation; their ability to regulate cytokine production by intracellular cytokine staining. Results: We found that T-regs are unable to regulate CD8 T-cell proliferation and cytokine production in patients studied at diagnosis, while they suppress CD8 T-cell proliferation and induce an elevation of IL-4 producing CD8 T-cells in patients during drug-induced remission. Conclusion: Inability of T-regs to regulate CD8 T-cell function at diagnosis may contribute to the initiation of autoimmune liver damage. The ability of T-regs to regulate CD8 proliferation and IL-4 production during drug-induced remission suggests a role for immunosuppressive treatment at reconstituting T-regs function. (c) 2005 Elsevier Ltd. All rights reserved.