IP-10 attracts T cells, NK cells, and monocytes to the site of infection thenthereby via the CXC chemokine receptor 3 (CXCR3) [17]. IP-10 is degraded into an antagonistic form by the dipeptidyl peptidase enzymatic activity of CD26 (also known as DPPIV), a serine protease that cleaves a dipeptide from the N-terminus of polypeptides with either a proline or alanine at the penultimate position [18], [19]. A recent study by Casrouge et al. reported that patients failing therapy have higher baseline plasma DPPIV activity [20]. The authors suggested that a subsequent systemic accumulation of the truncated antagonistic form of IP-10 impairs migration of CXCR3+ cells to the infected liver. CD26 is present both as a membrane-bound and as a soluble (sCD26) form, and the DPPIV activity of the membrane-bound form has been suggested to be important for T cell activation [21] possibly by associating with CD45 [22].

Also, sCD26 has been shown to enhance CD86 expression on antigen-presenting cells [23]. Dysfunctional exhausted HCV-specific T cells have been associated both with the establishment of HCV chronicity [24], [25] and with treatment failure following pegIFN-��-based therapy [26]. In line with these findings, functional HCV-specific T cell responses were observed in patients spontaneously resolving acute HCV infection [27] and in chronically infected patients achieving SVR following treatment [28]. The aim of the present study was to evaluate the impact of sCD26 on the outcome of HCV therapy and its association with the functionality of HCV-specific T cells.

Methods Ethical Aspects The treatment studies conformed to the guidelines of the 1975 Declaration of Helsinki and were approved by ethical committees at each center (Medicinska fakultetens forskningsetikkommitt��, G?teborgs Universitet, Gothenburg, Sweden, CPP-Ile-de-France IX, CHU Henri Mondor, Creteil, France, Comitato Etico Indipendente (IRB/IEC) dell’Azienda Ospedaliera di Parma, Parma, Italy, Comite d��Ethique du department de Medicine, Hopitaux Universitaires de Gen��ve, Geneva, Switzerland, the Helsinki committee of the Kaplan Medical Center, Rehovot, Israel, the Ethics Committee of Hospital General Vall d��Hebron, Barcelona, Spain, the Ethics Committee of Aristotle University of Thessaloniki, Thessaloniki, Greece, the Ethics Committee of Klinikum der Johann Wolfgang Goethe-Universitat, Frankfurt, Germany, and the Ethics Committee of University Hospital Rotterdam Dijkzigt, Rotterdam, Netherlands).

Written informed consent was obtained from each participating patient. Patients Between February 2001 and November 2003, 270 patients were recruited in a phase III, open-label, randomized, multicenter trial conducted by the DITTO-HCV study group at nine centers Drug_discovery in France, Germany, Greece, Israel, Italy, Netherlands, Spain, Sweden, and Switzerland, as previously reported [29].