Z Gastroenterol 2006; 44 - A92
DOI: 10.1055/s-2006-943458

The potential role of regulatory t cells and TGF-β1 in downregulating NKG2D killer activator receptor expression on cytotoxic cells in patients with chronic HCV hepatitis

G Pár 1, T Berki 2, L Pálinkás 2, L Szereday 3, M Halász 3, A Miseta 4, G Hegedűs 5, Z Faust 6, G Mózsik 1, B Hunyady 1, A Pár 1
  • 1Univ. of Pecs, First Dept. of Medicine
  • 2Dept. of Immunology
  • 3Dept. of Microbiology
  • 4Dept. of Laboratory Medicine
  • 5Baranya County Hosp.
  • 6Blood Transfusion Centre

Aims: Impaired natural killer (NK) cell activity has been proposed to contribute to viral persistence in HCV infection. Recent studies demonstrated that in tumors regulatory T cells (Treg) the secreted TGFβ1 down-regulates NKG2D killer activator receptor and NK cytotoxicity. Since in chronic hepatitis C plasma TGFβ1 level is also increased, we analyzed whether decreased NK activity corresponds to a dysregulated expression of NKG2D. Correlation between the percentage of Treg cells, TGFβ1 levels and NKG2D expression was also studied.

Methods: The percentage of peripheral CD4+CD25high+Treg cells, NKG2D+ NK and T cells were determined by FACS in 43 patients with chronic hepatitis C, in 10 sustained virological responders (SVR) and in 15 controls. Plasma levels of TGFβ1 were measured by ELISA.

Results: In chronic HCV hepatitis the killer activating receptor NKG2D expression was significantly downregulated both on NK (7.9 vs. 20.9%) and on T cells (18 vs. 26.3%) compared to controls. Impaired expression of NKG2D was associated with increased proportion of CD4+CD25high+ Treg cells (4.6 vs.3.1%) and increased TGFβ1 levels (15 vs.9 pg/ml) compared to controls. TGFβ1 levels inversely correlated with NKG2D expression on NK cells. In SVR group the percentage of Treg cells (1.7%), TGFβ1 levels (11.6 pg/ml) and NKG2D expression (NK: 17%, T: 20.9%) were comparable to healthy controls.

Conclusion: Our data suggest that TGFβ1 -secreted by regulatory T cells- may be responsible for impaired NK cell function via down-regulating NKG2D killer activating receptor in chronic HCV hepatitis. Thus, TGFβ1 antagonism or soluble NKG2D ligands may provide the basis of a novel antiviral or even cancer immunotherapy to improve the function of NK and T cells.