Directex vivo comparison of the breadth and specificity of the T cells in the liver and peripheral blood of patients with chronic HCV infection

Grabowska, Anna; Lechner, Franziska; Klenerman, Paul; Tighe, Paddy; Ryder, Stephen; Ball, JK; Thomson, Brian J.; Irving, William L.; Robins, R. A.

doi:10.1002/1521-4141(200108)31:8<2388::aid-immu2388>3.0.co;2-l

Cited by 115 publications

(84 citation statements)

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“…This concept of "original antigenic sin" has been shown to occur after sequential infection of mice with two similar strains of lymphocytic choriomeningitis virus, but has not been demonstrated in evolution from acute to chronic infection. 48 Anti-HCV immune responses may also be compartmentalized to the liver, as some studies suggest, [49][50][51] although others have found that specificities in the 2 compartments are similar, and studies of intrahepatic lymphocyte responses during acute human HCV infection are lacking. Recent evidence suggests that CD4ϩ T cell help is required for efficient development of effector and memory CD8 T cell populations in HIV infection, 52 and when lacking may facilitate viral escape mutation in HCV infection.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analyses of CD8+ T cell responses during longitudinal study of acute human hepatitis C

et al. 2005

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Section: Discussionmentioning

confidence: 99%

Comprehensive analyses of CD8+ T cell responses during longitudinal study of acute human hepatitis C

et al. 2005

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“…Hence, this specific subset of NKT cells may have an important role in HCV infection. It is noteworthy that compared to HCVspecific T cell infiltrates within inflamed HCV-infected livers [2,3], the CMV-and EBV-specific subsets are still relatively large and could potentially contribute to immunopathology through non-specific activation pathways.…”

Section: Discussionmentioning

confidence: 99%

“…However, in man, these studies have largely been restricted to blood for logistical reasons. In some cases, such as persistent viral hepatitis, the intrahepatic populations have been analyzed in a limited number of cases [2,3]. However, the interpretation of these results is difficult since no data exists on the relative distribution and phenotype of virusspecific T cell populations within an uninfected liver.…”

Section: Introductionmentioning

confidence: 99%

Virus‐specific CD8⁺ T lymphocytes within the normal human liver

et al. 2004

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The frequency and phenotype of human antiviral memory CD8 + T cells in blood are well studied, yet little is known about their distribution within tissues. Analysis of antiviral CD8 + T cell populations derived from a unique set of normal liver and blood samples identified a consistent population of virus-specific cells within the liver. In comparison to the circulating T cells, the liver-derived T cells were present at frequencies which were variably enriched compared to that in the blood, and showed significant differences with regard to the expression of CD45RA, CD45RO, CD95, CCR7, CD27 and CD28. The differences in these cell surface markers are consistent with a mature 'effector memory' phenotype of antigen-specific CD8 + T cells within the liver. An enrichment of an activated subset of NKT cells (V § 24/V g 11) was also observed, a finding which may be relevant to the regulation of the antiviral populations.

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“…97 Moreover, differences also exist between intrahepatic T cell responses and those in the peripheral blood. [98][99][100] However, strong, multispecific interferon gamma-producing, HCV-specific CD8 ϩ T cells are one of the characteristic features of patients who recover from an acute HCV infection. 66,68,69,72,[101][102][103][104][105][106][107][108][109][110][111][112][113][114] In a chronic HCV infection, although the frequencies of HCV-specific CD8 ϩ T cells may be normal, the cells exhibit a dysfunctional or stunned phenotype.…”

Section: Role Of Cd8 T Cellsmentioning

confidence: 99%

“…66,68,69,72,[101][102][103][104][105][106][107][108][109][110][111][112][113][114] In a chronic HCV infection, although the frequencies of HCV-specific CD8 ϩ T cells may be normal, the cells exhibit a dysfunctional or stunned phenotype. 66,100,115,116 Recent data indicate that most HCV-specific CD8 ϩ T cells express the inhibitory receptor programmed death 1 (PD-1) at the time of acute infection. 117 Interestingly, levels of PD-1 decline in patients with a resolved HCV infection but remain high during viral persistence.…”

Section: Role Of Cd8 T Cellsmentioning

confidence: 99%

Acute hepatitis C virus infection: A chronic problem

et al. 2007

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S ince the discovery of the hepatitis C virus (HCV) in the late 1980s, there has been an explosion of information regarding its natural history, treatment, and replication cycle. Nonetheless, there are still relatively few data regarding acute HCV infection. By convention, the term acute hepatitis refers to the presence of clinical signs or symptoms of hepatitis for a period of 6 months or fewer after the presumed time of HCV exposure. Early studies of posttransfusion patients who developed non-A, non-B hepatitis provide a clinical picture of early infection. 1 Following the availability of specific serologic and virologic tests, most such patients were shown to have acute HCV infection. After acute infection, HCV RNA may become detectable in the serum/plasma in as little as 2 weeks ( Fig. 1). Several weeks later, a high percentage of patients experience an increase in serum aminotransferase levels consistent with the development of acute hepatocellular injury. In the majority of cases, patients develop mild constitutional symptoms, including abdominal pain, nausea, vomiting, anorexia, and fatigue. During this acute infection, serum aminotransferases often peak below 1000 IU/mL and may return to normal levels. A minority develops sufficient elevations in bilirubin to lead to overt jaundice or the development of dark urine. Unless the clinical suspicion is high, few patients will be tested for HCV RNA or HCV antibody seroconversion. However, in the majority-but not all-of infected patients, HCV RNA persists, and a chronic disease state develops.The reasons for the general lack of data regarding acute HCV infection are multifactorial and include (1) the relatively high percentage of asymptomatic or unrecognized early infections, (2) the lack of large-scale identification of chronic carriers in the general population who serve as a reservoir for infection, and (3) the decreased number of acute infections that occur in controlled clinical settings such as that of blood transfusions. These factors and the lack of nonprimate animal models necessitate reliance on retrospective studies in chronic carriers, the use of limited historical collections of banked sera, and the extrapolation of outcomes based on small disease outbreaks in unique settings (for example, transmission from a physician to a patient in the operating room setting or following parenteral exposure in healthcare workers). Moreover, there exist only a limited number of population cohorts that continue to experience high rates of HCV transmission (for example, Egypt); nonetheless, there is a growing body of information regarding the clinical presentation, natural history, and treatment outcomes of acute HCV infection.In this article, we review the current information regarding our understanding of the epidemiology, virology, and immunology of HCV with a particular emphasis on acute HCV infection. In addition, we review recent data related to interferon-based treatment intervention and propose an algorithm for the diagnosis and management of acute HCV inf...

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Directex vivo comparison of the breadth and specificity of the T cells in the liver and peripheral blood of patients with chronic HCV infection

Cited by 115 publications

References 29 publications

Comprehensive analyses of CD8+ T cell responses during longitudinal study of acute human hepatitis C

Comprehensive analyses of CD8+ T cell responses during longitudinal study of acute human hepatitis C

Virus‐specific CD8⁺ T lymphocytes within the normal human liver

Acute hepatitis C virus infection: A chronic problem

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Directex vivo comparison of the breadth and specificity of the T cells in the liver and peripheral blood of patients with chronic HCV infection

Cited by 115 publications

References 29 publications

Comprehensive analyses of CD8+ T cell responses during longitudinal study of acute human hepatitis C

Comprehensive analyses of CD8+ T cell responses during longitudinal study of acute human hepatitis C

Virus‐specific CD8+ T lymphocytes within the normal human liver

Acute hepatitis C virus infection: A chronic problem

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Virus‐specific CD8⁺ T lymphocytes within the normal human liver