Vitamin D3 modulates T lymphocyte responses in hepatitis C virus-infected liver transplant recipients.

BACKGROUND: Aim of the present study was to investigate whether 1,25(OH)(2)D(3) (Vitamin D3) modulates T lymphocyte functions in patients transplanted for hepatitis C virus-related cirrhosis. METHODS: Sixteen patients and ten healthy subjects were investigated. T lymphocytes were activated in vitro in the presence or absence of Vitamin D3 and then the proliferative response and IFN-γ and TNF-α production were assessed. RESULTS: Vitamin D3 potently reduced T-lymphocyte proliferation in a dose-related fashion. Similarly, FACS analysis and ELISA testing demonstrated that Vitamin D3 significantly decreased the response frequency and the response intensity of IFN-γ and TNF-α production in the whole CD3-positive T lymphocyte population as well as in "naive" CD4+ CD45RA+ and "memory" CD4+ CD45RO+ T lymphocyte subsets. The inhibitory effect of Vitamin D3 on T-cell proliferation and cytokine production was not different between patients and controls. No toxic effects were exerted by Vitamin D3 even at the higher concentration used (10nM). Finally, no statistically significant correlation was found between 25(OH)D serum levels and the proliferative response or cytokine production of T lymphocytes from transplanted patients. CONCLUSIONS: This study demonstrates that in patients transplanted for hepatitis C virus-related cirrhosis Vitamin D3 modulates T lymphocyte activation, and provides a rationale for the evaluation of this compound as an immunosuppressive agent in liver-transplanted patients.