Recurrence of hepatitis C virus after loss of virus-specific CD4+ T-cell response in acute hepatitis C

Gerlach, J. Tilman; Diepolder, Helmut M.; Jung, Maria–Christina; Gruener, Norbert H.; Schraut, W.; Zachoval, Reinhart; Hoffmann, Robert M.; Schirren, C; Santantonio, T.; Pape, Gerd R.

doi:10.1016/s0016-5085(99)70353-7

Cited by 666 publications

(551 citation statements)

References 29 publications

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“…Data from other model viral infections, such as lymphoctic chorinomeningitis virus (LCMV), suggests that T cell exhaustion might result from a high rate of viral replication that exceeds the capacity of host immunity [129]. One mechanism of persistence in HCV is failure to maintain CD4+ T cells during early infection [91], which may be on the basis of high viral loads. Others have shown that HCV-specific CD8+ T cells in chronic infection are functionally impaired with respect to IFNγ production or anergic [93; 130; 131] and, consistent with this loss of function, exhibit phenotypic changes characteristic of early stages of differentiation [132].…”

Section: "Exhaustion"/anergymentioning

confidence: 99%

Immune responses during acute and chronic infection with hepatitis C virus

Ishii

Koziel

2008

Clinical Immunology

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Hepatitis C virus (HCV) induces persistent infection and causes chronic liver disease in most infected patients. Vigorous HCV-specific CD4+ and CD8+ T cell responses against HCV multiple epitopes are necessary for spontaneous viral clearance during the acute phase, but the virus appears to have multiple strategies to evade these defenses. There are relatively few studies on the role of immune responses during the chronic phase of infection. CD4+ T cell responses appear to protect against liver injury and may be important to clearance during interferon and ribavirin based therapy. Classic cytotoxic T cells (CTL) may primarily damage the liver in chronic HCV, but there may be subpopulations of T cells that protect against liver inflammation. Resolution of these outstanding questions is important to the development of a prophylactic vaccine as well as improving therapeutic options for those with chronic infection.

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Section: "Exhaustion"/anergymentioning

confidence: 99%

Immune responses during acute and chronic infection with hepatitis C virus

Ishii

Koziel

2008

Clinical Immunology

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“…There may be a state of 'instability' where virus may become undetectable in blood temporarily and then reappears [11].…”

Section: Clinical Featuresmentioning

confidence: 99%

“…• Clearance of acute infection in both man and in chimpanzee models is accompanied by strong CD4 + and CD8 + T cell responses against numerous HCV derived antigens [11,[13][14][15][16].…”

Section: Cellular Immunology Of Hcvmentioning

confidence: 99%

“…failure of T cell responses in the majority of patients, is not yet clear. Studies of those who go on to develop persistent infection have highlighted the weak CD4 + T cell responses, although it is not clear yet whether persistence of virus causes attenuation of T cell responses or vice versa [11,19,20]. Re-emergence of CD4 + T cell responses upon clearance of virus with interferon-alpha/ribavirin therapy suggests the latter -, i.e.…”

Section: Cellular Immunology Of Hcvmentioning

confidence: 99%

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Cellular immune responses against hepatitis C virus: the evidence base 2002

Ward¹,

Lauer

Isba³

et al. 2002

Clinical and Experimental Immunology

137

102

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SUMMARYHepatitis C virus (HCV) is an RNA virus which is estimated to persistently infect about 170 million people worldwide. After acute infection, there is an initial period during which long-term outcome is decided. There is strong evidence that the cellular immune responses, involving both CD4 + and CD8 + T lymphocytes, are involved at this stage and it is their effectiveness which determines outcome. What is not understood is what determines their effectiveness. The most important component of this is likely to be some aspect of epitope selection, itself dictated by host MHC. Thus, to understand host immunity to HCV, we need to have a detailed understanding of the peptides involved in T lymphocyte responses. In this review, we discuss the peptide epitopes that have been identified so far, and their potential significance. We relate this to a scheme of host defence which may be useful for understanding natural and vaccine-induced immunity.

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“…While a critical role for virus-specific CD4 + T cells in the induction and maintenance of effective immunity against HIV-1 is inferred from animal models and other human virus infections such as hepatitis C, direct evidence for this is lacking [10][11][12][13][14]. In healthy macaques, CD4 + T cell proliferation and TNF-a secretion were induced by DNA-prime/poxvirus-boost vaccinations, and were inversely correlated with control of SIV replication following a pathogenic challenge [15].…”

Section: Introductionmentioning

confidence: 99%

Immunisation with recombinant modified vaccinia virus Ankara expressing HIV‐1 gag in HIV‐1‐infected subjects stimulates broad functional CD4⁺ T cell responses

et al. 2006

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Virus-specific CD4 + T cells with IL-2-secreting and/or proliferative capacity are detected readily in HIV-1-infected long-term nonprogressors and rarely in persons with untreated progressive infection. The contribution of these cells to viraemia control is uncertain, but this question might be addressed in clinical therapeutic vaccination studies. However, the quality of T helper responses induced by currently available HIV-1 vaccine candidates has not been explored in depth. We determined the effect of vaccination with modified vaccinia virus Ankara (MVA) expressing HIV-1 gag p24/p17 (MVA.HIVA) on HIV-1-specific CD4 + T cell responses in 16 chronically infected, highly active antiretroviral therapy (HAART)-treated subjects using CD8-depleted IFN-c ELISPOT assays, intracellular cytokine staining assays for IL-2 and IFN-c, and a CFSEbased proliferation assay. Gag-specific CD4 + T cell responses were significantly increased in magnitude and breadth after vaccination and targeted both known and new epitopes, several of which were also recognised by healthy HIV-uninfected volunteers immunised with the same vaccines. The frequencies of CD4 + T cells expressing IL-2 or IFN-c, alone or simultaneously, were also augmented. These findings indicate that functional virus-specific T helper cells can be boosted by vaccination in chronic HIV-1 infection. Further evaluation of their role in viraemia control is warranted. IntroductionThe rate of progression of HIV-1 infection to AIDS may be determined by the capacity for immunological recovery after early and extensive depletion of mucosal CD4 + T cells [1]. Highly active antiretroviral therapy (HAART) can restore CD4 + T cell-mediated responses to opportunistic pathogens, but maintenance of adequate CD4 + T cell counts requires lifelong antiretroviral therapy, which is associated with potentially serious adverse effects and is too costly for the majority of infected persons worldwide [2]. Furthermore, the capacity of HIV-1-specific CD4 + T cells to proliferate and secrete IL-2, characteristics which are typically preserved only in long-term nonprogressors, are not always restored after initiation of therapy, particularly when this is delayed beyond acute infection [3][4][5][6]. Loss of function may result from preferential infection of virus-specific cells by 7,8]. Enhancement of HIV-1-specific cellular responses by therapeutic vaccination in combination with fully suppressive antiretroviral therapy might be used to maintain HIV-1 control without continuous drug treatment [9]. While a critical role for virus-specific CD4 + T cells in the induction and maintenance of effective immunity against HIV-1 is inferred from animal models and other human virus infections such as hepatitis C, direct evidence for this is lacking [10][11][12][13][14]. In healthy macaques, CD4 + T cell proliferation and TNF-a secretion were induced by DNA-prime/poxvirus-boost vaccinations, and were inversely correlated with control of SIV replication following a pathogenic challenge [15]. In humans, cross-...

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Recurrence of hepatitis C virus after loss of virus-specific CD4+ T-cell response in acute hepatitis C

Cited by 666 publications

References 29 publications

Immune responses during acute and chronic infection with hepatitis C virus

Immune responses during acute and chronic infection with hepatitis C virus

Cellular immune responses against hepatitis C virus: the evidence base 2002

Immunisation with recombinant modified vaccinia virus Ankara expressing HIV‐1 gag in HIV‐1‐infected subjects stimulates broad functional CD4⁺ T cell responses

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Recurrence of hepatitis C virus after loss of virus-specific CD4+ T-cell response in acute hepatitis C

Cited by 666 publications

References 29 publications

Immune responses during acute and chronic infection with hepatitis C virus

Immune responses during acute and chronic infection with hepatitis C virus

Cellular immune responses against hepatitis C virus: the evidence base 2002

Immunisation with recombinant modified vaccinia virus Ankara expressing HIV‐1 gag in HIV‐1‐infected subjects stimulates broad functional CD4+ T cell responses

Contact Info

Product

Resources

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Immunisation with recombinant modified vaccinia virus Ankara expressing HIV‐1 gag in HIV‐1‐infected subjects stimulates broad functional CD4⁺ T cell responses