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 tumorspecificantigens. several studies suggest that suppression of tumor-associated antigen reactivates lymphocytes bycd4+ cd25+ regulatory t (t,eg) cells. this study was designed to evaluate whether cd4+cd25+ t'9 cells in chronic liverdisease and hepatocellular carcinoma (hcc) patients exhibit an expanded t,og pool and to correlate it with liver tumormarkers and grading.methods: blood samples were collected from 20 patients with cirrhotic liver disease (cld), 15 hcc patients and 10healthy control subjects. alpha fem-protein (afp), hbv and hcv antibodies were detected by eia. hcv was confirmedby immunoblotting and rt-pcr. to evaluate hccgrading, abdominal ultrasound guided liver biopsy was done. patientswere categorized into moderately differentiated (grade ii) and poorly differentiated (grade iii) groups. cytometricanalysis of cd4+cd25+ treg cells in pbmcs was performed using anti-cd3, anti-cd4, anti-cd25, anti-cd45ra, and iggisotypecontrol (filc and pel.results: both cld and hcc groups were 80% positive for hcv while only 20% of cld and 11% of hcc patients werepositive for hbv. the mean percentage of cd4+cd25+t cell population demonstrated a highly significant increase incomparing 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 cellspercentage was 9.12(plus-minus)1.52 and 8.73(plus-minus)1.33, respectively. a negative correlation was found between mean cd4+cd25+ tcells 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 theunique marker afp and with tumor grades. better understanding of the underlying mechanism of t,.g regulation or ofthe strategy for controlling t'g cells may lead to effective hcv immunotherapy and enhancing immunity against cancer.