Effect of CD4+ CD25+ regulatory T-cells on CD8 T-cell function in patients with autoimmune hepatitis
MS Longhi, Y Ma, RR Mitry, DP Bogdanos… - Journal of …, 2005 - Elsevier
Journal of Autoimmunity, 2005•Elsevier
BACKGROUND AND AIMS: CD4 T lymphocytes constitutively expressing the IL-2-receptor α-
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 IFNγ 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 …
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 IFNγ 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 …
BACKGROUND AND AIMS
CD4 T lymphocytes constitutively expressing the IL-2-receptor α-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 IFNγ 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 3H-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.
Elsevier