Assessment of Treg Cells CD4+CD25+ in Chronic Cirrhotic Liver Disease and Hepatocellular Carcinoma Egyptian Patients

Background and Aims: Dysfunction of the host immune system in cancer patients can be due to a number of factors, including secretion of tumor-derived immunosuppressive factors or induction of immune tolerance against tumorspecific antigens. Several studies suggest that suppression of tumor-associated antigen reactivates lymphocytes by CD4+ CD25+ regulatory T (T,eg) cells. This study was designed to evaluate whether CD4+CD25+ T 9 cells in chronic liver disease and hepatocellular carcinoma (HCC) patients exhibit an expanded T,og pool and to correlate it with liver tumor markers and grading. Methods: Blood samples were collected from 20 patients with cirrhotic liver disease (CLD), 15 HCC patients and 10 healthy control subjects. Alpha fem-protein (AFP), HBV and HCV antibodies were detected by EIA. HCV was confirmed by immunoblotting and RT-PCR. To evaluate HCCgrading, abdominal ultrasound gUided liver biopsy was done. Patients were categorized into moderately differentiated (grade II) and poorly differentiated (grade III) groups. Cytometric analysis of CD4+CD25+ Treg cells in PBMCs was performed using anti-CD3, anti-CD4, anti-CD25, anti-CD45RA, and IgGisotype control (FIlC and PEl. Results: Both CLD and HCC groups were 80% positive for HCV while only 20% of CLD and 11% of HCC patients were positive for HBV. The mean percentage of CD4+CD25+T cell population demonstrated a highly significant increase in comparing HCV to HCC patients [2.47(PLUS-MINUS)0.66 vs. 8.96(PLUS-MINUS)1.38 (P(LESS THAN)0.001)] and when comparing both group to controls [1.15(PLUS-MINUS)0.5 (P(LESS THAN)0.01)]. Nine HCC patients were in grade II while 6/15 were in grade III. Their mean CD4+CD25+ T cells percentage was 9.12(PLUS-MINUS)1.52 and 8.73(PLUS-MINUS)1.33, respectively. A negative correlation was found between mean CD4+CD25+ T cells percentage and AFP serum level in HCCpatients (r=-0.923) while Treg cells with patients tumor grades (II and III) (r=0.474 and 0.582, respectively). CLD showed a significant correlation with AFP level (r= 0.962). Conclusions: Tumor specific T,eg cells may limit the efficacy of anti-tumor response. T,eg cells correlate properly with the unique marker AFP and with tumor grades. Better understanding of the underlying mechanism of T,.g regulation or of the strategy for controlling T g cells may lead to effective HCV immunotherapy and enhancing immunity against cancer.