HIV Coinfection Impairs CD28‐Mediated Costimulation of Hepatitis C Virus–Specific CD8 Cells

Yonkers, Nicole L.; Rodrı́guez, Benigno; Post, Anthony B.; Asaad, Robert; Jones, Linda; Lederman, Michael M.; Lehmann, Paul; Anthony, Donald D.

doi:10.1086/505582

Cited by 13 publications

(18 citation statements)

References 63 publications

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“…On the other hand, HCV-specific CD8 ϩ T cells have an earlier memory phenotype (i.e., CD28 ϩ CD27 ϩ ), whereas CMV-specific T cells have a late effector phenotype (i.e., CD27 Ϫ 28 Ϫ ) [9]. Our current study confirms previously reported findings that HIV ϩ persons have fewer CD8 ϩ CD28 ϩ T cells than do HIV Ϫ persons, whereas HCV ϩ persons have more CD8 ϩ CD28 ϩ T cells than do HCV Ϫ persons [8,12,13]. Additionally, we found that HIV ϩ HCV ϩ RNA ϩ women have increased CD8 ϩ 28 ϩ HLA-DR ϩ T cells.…”

Section: Immune Activation Is a Hallmark Of Human Immunodeficiency VIsupporting

confidence: 90%

“…We previously published the finding that coinfected women have increased primed activated T cells (i.e., CD8 ϩ CD45RO ϩ CD27 ϩ 95 ϩ ), compared with HIV ϩ HCV Ϫ women [6], and postulated that this population of cells represented effector/central memory T cells. The population of activated CD8 ϩ 28 ϩ cells in our current study may also represent early central memory T cells and further suggests that HCV may be playing a role in skewing CD8 ϩ maturation toward an earlier phenotype [6,9,[11][12][13].…”

Section: Immune Activation Is a Hallmark Of Human Immunodeficiency VImentioning

confidence: 57%

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CD8⁺T Cell Activation in Women Coinfected with Human Immunodeficiency Virus Type 1 and Hepatitis C Virus

Kovács¹,

Al‐Harthi

Christensen³

et al. 2008

J INFECT DIS

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Immune activation is a hallmark of human immunodeficiency virus type 1 (HIV-1) infection and impacts innate and adaptive immunity. Individuals coinfected with HIV-1 and hepatitis C virus (HCV) may have increased immune activation early in HIV disease because of a high HCV antigen load in tissues such as the liver. We evaluated T cell markers of activation and maturation in women with or without HIV-1 infection, by HCV antibody and HCV RNA status. We found increased percentages of activated CD8(+) T cells (i.e., CD8(+)HLA-DR(+)38(+) cells and CD8(+)CD28(+)HLA-DR(+) cells) but not of CD4(+) T cells among women who tested positive for HIV-1, HCV antibody, and HCV RNA, compared with HIV-1-positive women who tested negative for HCV antibody. Because CD8(+) T cell activation is related to HIV-1 disease progression, these data may have implications for the medical management of patients coinfected with HIV-1 and HCV.

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Section: Immune Activation Is a Hallmark Of Human Immunodeficiency VIsupporting

confidence: 90%

Section: Immune Activation Is a Hallmark Of Human Immunodeficiency VImentioning

confidence: 57%

CD8⁺T Cell Activation in Women Coinfected with Human Immunodeficiency Virus Type 1 and Hepatitis C Virus

Kovács¹,

Al‐Harthi

Christensen³

et al. 2008

J INFECT DIS

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“…Notably, we did not distinguish between CD4 and CD8 responses in these assays, so we cannot comment on whether this compartmentalization encompasses CD4, CD8, or both subsets of T cells. Our demonstration of HCV-specific T-cell responses within the IHL and PBL compartments in under half of the subjects is similar to responses previously found in the PBL compartment of chronic HCVinfected patients with compensated liver function, using the same assay method (47). This underscores the paucity of IFN-␥-producing T cells previously described for the PBL compartment (16,24,25,(42)(43)(44) and extends the observation to the IHL compartment in the setting of direct ex vivo assays.…”

Section: Vol 82 2008 Liver and Perihepatic Lymph Node Lymphocytes 1supporting

confidence: 87%

“…Proliferative function was measured by thymidine incorporation. The use of 10 pools of HCV peptides allows for analysis of the HCV-specific immune response to 441 possible 18-mer peptides with a limited number of cells (47). Mitogen-induced IFN-␥ and proliferation responses were measured to ensure cell viability.…”

Section: Resultsmentioning

confidence: 99%

Hepatitis C Virus-Specific T-Cell Gamma Interferon and Proliferative Responses Are More Common in Perihepatic Lymph Nodes than in Peripheral Blood or Liver

Moonka

Milkovich

Rodrı́guez

et al. 2008

J Virol

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The activation state, differentiation state, and functions of liver lymphocytes and perihepatic lymph nodes during chronic hepatitis C virus (HCV) infection are not well understood. Here, we performed phenotypic and functional analyses of freshly prepared lymphocytes isolated from the livers, perihepatic lymph nodes, and peripheral blood compartments of chronic HCV-infected and disease control subjects with end-stage liver disease undergoing liver transplantation. We measured lymphocyte subset frequency and memory T-cell gamma interferon (IFN-␥) and proliferative responses to HCV peptide and control viral antigens in direct ex vivo assays. We found higher frequencies of CD4 cells in the lymph node compartment than in the other compartments for both HCV-infected and disease control subjects. Lymph node CD4 and CD8 cells less commonly expressed the terminal differentiation marker CD57, a finding consistent with an earlier differentiation state. In HCV-infected subjects, HCV-specific IFN-␥-producing and proliferative responses were commonly observed in the lymph node fraction, while they were uncommonly observed in the peripheral blood or liver fractions. In contrast, control viral CD4 protein antigen and CD8 peptide antigen-specific IFN-␥ responses were commonly observed in the periphery and uncommonly observed in the lymph nodes of these same subjects. These findings are consistent with a selective defect in HCV-specific T-cell effector function or distribution in patients with advanced chronic HCV infection. The high frequency of HCV-reactive T cells in perihepatic lymph nodes indicates that a failure to generate or sustain T-lymphocyte HCV reactivity is not responsible for the paucity of functional cells even in end-stage liver disease.During hepatitis C virus (HCV) infection, both CD4 and CD8 virus-specific lymphocytes are thought to play important roles both in control/clearance of viral infection and in hepatocellular damage (7,9,13,23,26,32,33,37,38,40). Priming of these cells during acute infection and sustained activation of memory cells during chronic infection are thought to take place in regional lymph nodes that drain the tissue sites of infection. Chronic HCV infection is characterized by low frequencies of HCV-reactive T cells in circulation (16,34,(42)(43)(44). While there are a number of potential explanations for these meager responses, the relative distribution levels of HCVreactive T cells in lymph nodes, liver, and peripheral blood are not well recognized. We therefore examined the phenotype and function of HCV-specific T cells within the regional lymph nodes, livers, and peripheral blood of HCV-infected individuals, using freshly isolated tissue samples in order to obtain an improved understanding of the dominant T-cell dynamics during HCV infection and to establish a foundation for improved models of compartmentalized T-cell activation during chronic viral hepatitis. Results indicate similar paucities of functional HCV-specific T cells in the liver and periphery, while HCVreactive T cells ar...

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“…Liver fibrosis progression may be related to weak cellular immune responses to HCV antigens in HIV infected patients. HIV infection is characterized by marked decreases in the number of circulating CD4 cells, functional impairment of both CD4 and CD8 cells and down-regulation of CD28 expression (a costimulatory molecule required for effective lymphocyte activation) [102]. Patients with lower CD4 cells have less HCV specific CD8 cells responses and this could explain the more advanced liver disease progression since CD8 cells responses are thought to be of primary importance in the immune response to viral infection.…”

Section: Epidemiologymentioning

confidence: 99%

HIV Co-Infections with Hepatitis B and C

Singhatiraj

Suri²,

Goulston³

2013

J AIDS Clin Res

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HIV Coinfection Impairs CD28‐Mediated Costimulation of Hepatitis C Virus–Specific CD8 Cells

Cited by 13 publications

References 63 publications

CD8⁺T Cell Activation in Women Coinfected with Human Immunodeficiency Virus Type 1 and Hepatitis C Virus

CD8⁺T Cell Activation in Women Coinfected with Human Immunodeficiency Virus Type 1 and Hepatitis C Virus

Hepatitis C Virus-Specific T-Cell Gamma Interferon and Proliferative Responses Are More Common in Perihepatic Lymph Nodes than in Peripheral Blood or Liver

HIV Co-Infections with Hepatitis B and C

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HIV Coinfection Impairs CD28‐Mediated Costimulation of Hepatitis C Virus–Specific CD8 Cells

Cited by 13 publications

References 63 publications

CD8+T Cell Activation in Women Coinfected with Human Immunodeficiency Virus Type 1 and Hepatitis C Virus

CD8+T Cell Activation in Women Coinfected with Human Immunodeficiency Virus Type 1 and Hepatitis C Virus

Hepatitis C Virus-Specific T-Cell Gamma Interferon and Proliferative Responses Are More Common in Perihepatic Lymph Nodes than in Peripheral Blood or Liver

HIV Co-Infections with Hepatitis B and C

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CD8⁺T Cell Activation in Women Coinfected with Human Immunodeficiency Virus Type 1 and Hepatitis C Virus

CD8⁺T Cell Activation in Women Coinfected with Human Immunodeficiency Virus Type 1 and Hepatitis C Virus