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


CONCLUSIONS
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.
Longhi
Maria Serena
MS
Institute of Liver Studies, King's College London, King's College Hospital, Denmark Hill, London SE5 9RS, UK.
Ma
Yun
Y
Mitry
Ragai R
RR
Bogdanos
Dimitrios P
DP
Heneghan
Michael
M
Cheeseman
Paul
P
Mieli-Vergani
Giorgina
G
Vergani
Diego
D
D016516:CD4-CD8 Ratio; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D049109:Cell Proliferation; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis; D003602:Cytotoxicity, Immunologic; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D051858:Forkhead Transcription Factors; D019693:Hepatitis, Autoimmune / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism
D016207:Cytokines; D004268:DNA-Binding Proteins; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors