Regulation of T cell recruitment and inflammation in the human immunodeficiency virus/hepatitis C virus coinfected liver
Background and Aim: Patients coinfected with both hepatitis C virus (HCV) and human immunodeficiency virus (HIV) have accelerated liver disease compared with HCV monoinfected patients. In chronic HCV infection, it is known that chemokines play a key role in T cell recruitment and in determining the extent of hepatic injury. Methods: In this study, we determined by quantitative real-time reverse transcriptase polymerase chain reaction and immunohistochemistry the intrahepatic phenotype of the cellular infiltrate and its associated chemokine profile and localization in a cohort of relatively immune competent coinfected HIV/HCV subjects. Results: Increased lobular expression of CD8+ cytotoxic T cells was found in the coinfected liver in conjunction with increased expression of the T cell chemoattractant, chemokine (C-C motif) ligand (CCL) 5, compared with the HCV mono-infected liver. Furthermore, the number of lobular-infiltrating CD8+ T cells was positively correlated with the expression of CCL5. Immunohistochemical staining of CCL5 showed it to primarily localize to the hepatocytes. Within the inflammatory infiltrate, proliferating (Ki-67+) and apoptotic terminal deoxynucleotidyl transferase 2'-deoxyuridine 5'-triphosphate nick end labeling + (TUNEL)+ cells were sparse. Conclusions: Collectively, the data suggest that even in the setting of relatively immune competent coinfected subjects, a pro-inflammatory milieu exists, which can potentially drive the increased T cell recruitment found in the HIV/HCV coinfected liver. This profile is likely to contribute to the accelerated progression of liver disease observed in HIV/HCV coinfection.
|Authors||Nguyen, N. ; Hampartzoumian, T. ; Cameron, B. ; Palmer, C. ; O'Toole, S. ; Post, J. ; Zekry, A. ; Lloyd, A.;|
|Publisher Name||JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY|
|URL link to publisher's version||<Go to ISI>://WOS:000340419500030|
|OpenAccess link to author's accepted manuscript version||https://publications.gimr.garvan.org.au/open-access/12739|