Accumulation of dysfunctional effector CD8+T cells in the liver of patients with chronic HCV infection. Export

@article{citeulike:484861, abstract = {BACKGROUND/AIMS: Hepatitis C virus (HCV) causes a chronic infection that can lead to fibrosis and carcinoma. Immune responses mediated by cytotoxic T lymphocytes (CTLs) could be involved in viral clearance or persistence, and therefore in determining the course of the disease. METHODS: Intrahepatic and peripheral blood CD8+T cells were obtained from 32 HCV-chronically infected patients and analysed by flow-cytometry for surface markers of differentiation, IFNgamma and TNFalpha production, degranulation capacity and perforin content, after CD3 triggering. Results were compared with those obtained from 13 patients with a non-viral liver disease. RESULTS: Intrahepatic CD8+T cells of HCV-infected patients, despite their phenotype of pre-terminally and terminally differentiated effectors (CCR7-CD45RA-/+), are poorly responsive to T cell receptor (TCR)-mediated stimulation compared with those obtained from uninfected subjects. This defect correlates with the severity of fibrosis, is more pronounced in patients with ALT<1.5xN than with ALT>1.5xNU/ml, and is not evident after mitogen stimulation. CONCLUSIONS: The present study describes the accumulation of hypo-responsive CD8+T cells in the liver of patients with chronic HCV infection. Understanding the mechanisms underlying this impairment may be helpful in the design of innovative strategies for HCV treatment.}, address = {National Institute for Infectious Diseases IRCCS 'L. Spallanzani', Via Portuense 292, 00149 Rome, Italy.}, author = {Nisii, Carla and Tempestilli, Massimo and Agrati, Chiara and Poccia, Fabrizio and Tocci, Guido and Longo, Maria Antonella A. and D'Offizi, Gianpiero and Tersigni, Roberto and Iacono, Oreste Lo L. and Antonucci, Giorgio and Oliva, Alessandra}, citeulike-article-id = {484861}, citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.jhep.2005.10.023}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/16426698}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=16426698}, day = {5}, doi = {10.1016/j.jhep.2005.10.023}, issn = {0168-8278}, journal = {J Hepatol}, keywords = {cd8, dysfunction, hcv}, month = {December}, posted-at = {2006-01-29 17:47:29}, priority = {3}, title = {Accumulation of dysfunctional effector CD8+T cells in the liver of patients with chronic HCV infection.}, url = {http://dx.doi.org/10.1016/j.jhep.2005.10.023}, year = {2005} }

TY - JOUR ID - citeulike:484861 L3 - citeulike-article-id:484861 N2 - BACKGROUND/AIMS: Hepatitis C virus (HCV) causes a chronic infection that can lead to fibrosis and carcinoma. Immune responses mediated by cytotoxic T lymphocytes (CTLs) could be involved in viral clearance or persistence, and therefore in determining the course of the disease. METHODS: Intrahepatic and peripheral blood CD8+T cells were obtained from 32 HCV-chronically infected patients and analysed by flow-cytometry for surface markers of differentiation, IFNgamma and TNFalpha production, degranulation capacity and perforin content, after CD3 triggering. Results were compared with those obtained from 13 patients with a non-viral liver disease. RESULTS: Intrahepatic CD8+T cells of HCV-infected patients, despite their phenotype of pre-terminally and terminally differentiated effectors (CCR7-CD45RA-/+), are poorly responsive to T cell receptor (TCR)-mediated stimulation compared with those obtained from uninfected subjects. This defect correlates with the severity of fibrosis, is more pronounced in patients with ALT<1.5xN than with ALT>1.5xNU/ml, and is not evident after mitogen stimulation. CONCLUSIONS: The present study describes the accumulation of hypo-responsive CD8+T cells in the liver of patients with chronic HCV infection. Understanding the mechanisms underlying this impairment may be helpful in the design of innovative strategies for HCV treatment. JF - J Hepatol SN - 0168-8278 AD - National Institute for Infectious Diseases IRCCS ‘L. Spallanzani’, Via Portuense 292, 00149 Rome, Italy. TI - Accumulation of dysfunctional effector CD8+T cells in the liver of patients with chronic HCV infection. KW - cd8 KW - dysfunction KW - hcv AU - Nisii, Carla AU - Tempestilli, Massimo AU - Agrati, Chiara AU - Poccia, Fabrizio AU - Tocci, Guido AU - Longo, Maria Antonella AU - D'Offizi, Gianpiero AU - Tersigni, Roberto AU - Iacono, Oreste Lo AU - Antonucci, Giorgio AU - Oliva, Alessandra PY - 2005/12/05/ UR - http://dx.doi.org/10.1016/j.jhep.2005.10.023 ER -