Increased expression of regulatory Tr1 cells in recurrent hepatitis C after liver transplantation.
Immune response failure during HCV infection has been associated with the activity of regulatory T cells. Hepatitis C-related cirrhosis is the main reason for liver transplantation. However, 80% of transplanted patients present an accelerated recurrence of the disease. This study assessed the involvement of regulatory T-cell subsets (CD4+CD25+ cells: 'Treg' and CD49b+CD18+ cells: 'T regulatory-1' cells), in the recurrence of HCV after liver transplantation, using transcriptomic analysis, ELISA assays on serum samples and immunohistochemistry on liver biopsies from liver recipients 1 and 5 years after transplantation. Three groups of patients were included: stable HCV-negative recipients and those with mild and severe hepatitis C recurrence. At 5 years, Treg markers were overexpressed in all HCV+ recipients. By contrast, Tr1 markers were only overexpressed in patients with severe recurrence. At 1 year, a trend toward the overexpression of Tr1 was noted in patients evolving toward severe recurrence. IL-10 production, a characteristic of the Tr1 subset, was enhanced in severe recurrence at both 1 and 5 years. These results suggest that Tr1 are enhanced during severe HCV recurrence after liver transplantation and could be predictive of HCV recurrence. High levels of IL-10 at 1 year could be predictive of severe recurrence, and high IL-10 producers might warrant more intensive management.
Carpentier
A
A
Laboratoire de Biologie Cellulaire, Université René Descartes, Paris, France.
Conti
F
F
Stenard
F
F
Aoudjehane
L
L
Miroux
C
C
Podevin
P
P
Morales
O
O
Chouzenoux
S
S
Scatton
O
O
Groux
H
H
Auriault
C
C
Calmus
Y
Y
Pancre
V
V
Delhem
N
N
D000328:Adult; D018821:CD18 Antigens / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D015967:Gene Expression Regulation, Viral; D006526:Hepatitis C / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D039421:Integrin alpha2 / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis; D016031:Liver Transplantation / Q000379:methods*; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism*
D018821:CD18 Antigens; D039421:Integrin alpha2; D053645:Interleukin-2 Receptor alpha Subunit; D016753:Interleukin-10