2010
Vali, Bahareh; Jones, R. Brad; Sakhdari, Ali; Sheth, Prameet M.; Clayton, Kiera; Yue, Feng-Yun; Gyenes, Gabor; Wong, David; Klein, Marina B.; Saeed, Sahar; Benko, Erika; Kovacs, Colin; Kaul, Rupert; Ostrowski, Mario A.
In: European Journal of Immunology, vol. 40, no. 9, pp. 2493-2505, 2010.
Abstract | Links | BibTeX | Tags: HIV-HCV co-infection, Liver disease, T-cell exhaustion
@article{Vali2010,
title = {HCV-specific T cells in HCV/HIV Co-infection show elevated frequencies of dual Tim-3/PD-1 expression that correlate with liver disease progression},
author = {Bahareh Vali and R. Brad Jones and Ali Sakhdari and Prameet M. Sheth and Kiera Clayton and Feng-Yun Yue and Gabor Gyenes and David Wong and Marina B. Klein and Sahar Saeed and Erika Benko and Colin Kovacs and Rupert Kaul and Mario A. Ostrowski},
url = {https://www.ncbi.nlm.nih.gov/pubmed/20623550},
doi = {10.1002/eji.201040340},
year = {2010},
date = {2010-09-01},
journal = {European Journal of Immunology},
volume = {40},
number = {9},
pages = {2493-2505},
abstract = {Co-infection of HCV with HIV has been associated with more rapid progression of HCV-related disease. HCV-specific T-cell immune responses, which are essential for disease control, are attenuated in co-infection with HIV. T-cell exhaustion has recently been implicated in the deficient control of chronic viral infections. In the current study, we investigated the role of programmed death-1 (PD-1) and T-cell immunoglobulin and mucin domain-containing molecule-3 (Tim-3) expression in T-cell exhaustion during HCV/HIV co-infection. We show that in HCV/HIV co-infection, both total and HCV-specific T cells co-express Tim-3 and PD-1 in significantly higher frequencies, compared with HCV mono-infection. Co-expression of these two markers on HCV-specific CD8(+) T cells positively correlated with a clinical parameter of liver disease progression. HCV-specific CD8(+) T cells showed greater frequencies of Tim-3/PD-1 co-expression than HIV-specific CD8(+) T cells, which may indicate a greater degree of exhaustion in the former. Blocking Tim-3 or PD-1 pathways restored both HIV- and HCV-specific CD8(+) T-cell expansion in the blood of co-infected individuals. These data demonstrate that co-expression of Tim-3 and PD-1 may play a significant role in HCV-specific T-cell dysfunction, especially in the setting of HIV co-infection.},
keywords = {HIV-HCV co-infection, Liver disease, T-cell exhaustion},
pubstate = {published},
tppubtype = {article}
}
Co-infection of HCV with HIV has been associated with more rapid progression of HCV-related disease. HCV-specific T-cell immune responses, which are essential for disease control, are attenuated in co-infection with HIV. T-cell exhaustion has recently been implicated in the deficient control of chronic viral infections. In the current study, we investigated the role of programmed death-1 (PD-1) and T-cell immunoglobulin and mucin domain-containing molecule-3 (Tim-3) expression in T-cell exhaustion during HCV/HIV co-infection. We show that in HCV/HIV co-infection, both total and HCV-specific T cells co-express Tim-3 and PD-1 in significantly higher frequencies, compared with HCV mono-infection. Co-expression of these two markers on HCV-specific CD8(+) T cells positively correlated with a clinical parameter of liver disease progression. HCV-specific CD8(+) T cells showed greater frequencies of Tim-3/PD-1 co-expression than HIV-specific CD8(+) T cells, which may indicate a greater degree of exhaustion in the former. Blocking Tim-3 or PD-1 pathways restored both HIV- and HCV-specific CD8(+) T-cell expansion in the blood of co-infected individuals. These data demonstrate that co-expression of Tim-3 and PD-1 may play a significant role in HCV-specific T-cell dysfunction, especially in the setting of HIV co-infection.
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