Premium
Quantification of hepatic FOXP 3+ T ‐lymphocytes in HIV /hepatitis C coinfection
Author(s) -
Williams S. K.,
Donaldson E.,
Kleij T.,
Dixon L.,
Fisher M.,
Tibble J.,
Gilleece Y.,
Klenerman P.,
Banham A. H.,
Howard M.,
Webster D. P.
Publication year - 2014
Publication title -
journal of viral hepatitis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 100
eISSN - 1365-2893
pISSN - 1352-0504
DOI - 10.1111/jvh.12141
Subject(s) - coinfection , human immunodeficiency virus (hiv) , medicine , virology
Summary Coinfection with HIV adversely impacts every stage of hepatitis C ( HCV ) infection. Liver damage in HCV infection results from host antiviral responses rather than direct viral pathogenesis. Despite depressed cellular immunity, coinfected patients show accelerated hepatic fibrosis compared with HCV monoinfected patients. This paradox is poorly understood. T ‐regulatory (Treg) cells ( CD 4+ and FOXP 3+) are hypothesized to limit hepatic damage in HCV . Our hypothesis was that reduced frequency of hepatic T reg in HIV / HCV coinfection compared with HCV monoinfection may explain poorer outcomes. We quantified FOXP 3+, CD 4+, CD 8+ and CD 20+ cells in liver biopsies of 35 male subjects matched by age and ISHAK fibrosis score, 12 HIV monoinfected, 11 HCV monoinfected and 12 HIV / HCV coinfected. Cell counts were performed using indirect immunohistochemical staining and light microscopy. HIV / HCV coinfected subjects had fewer hepatic FOXP 3+ ( P = 0.031) and CD 4+ cells ( P = 0.001) than HCV monoinfected subjects. Coinfected subjects had more hepatic CD 8+ cells compared with HCV monoinfected ( P = 0.023), and a lower ratio of FOXP 3+ to CD 8+ cells (0.08 vs 0.27, P < 0.001). Multivariate analysis showed number of CD 4+ cells controlled for differences in number of FOXP 3+ cells. Fewer hepatic FOXP 3+ and CD 4+ cells in HIV / HCV coinfection compared with HCV monoinfection suggests lower T reg activity, driven by an overall loss of CD 4+ cells. Higher number of CD 8+ cells in HIV / HCV coinfection suggests higher cytotoxic activity. This may explain poorer outcomes in HIV / HCV coinfected patients and suggests a potential mechanism by which highly active antiretroviral therapy may benefit these patients.