Increased frequency of CD8+ CD45R0+ memory T lymphocytes in acute hepatitis B virus infection

Jung, Maria–Christina; Schraut, W.; Santantonio, T.; Spengler, Ulrich; Eichenlaub, D.; Eisenburg, J; Zachoval, R.; Hoffmann, Robert M.; Paumgartner, Gustav; Pastore, Giuseppe; H, Will; Riethmüller, Gert; Ziegler-Heitbrock, Hans-Werner Löins; Pape, G.

doi:10.1016/s0168-8278(05)80273-9

Cited by 19 publications

(9 citation statements)

References 12 publications

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“…Our results are in agreement with those of Jung et al [28], who also found that peripheral blood CD4 + numbers were reduced in patients with chronic HBV com-pared to controls, although the precise biochemical and virological status of the patients at the time of sampling were not defined. Interestingly, these authors also noted a persistence in the reduction of CD4 + percentages in the HBV-infected group, although whether these patients seroconverted or continued to experience recurrent disease exacerbations was not shown.…”

Section: Discussionsupporting

confidence: 93%

“…In agreement with others [28,30], we also saw no correlation between any of the groups with respect to changes in percentages of T-cell subsets bearing activated markers, such as CD45RO, HLA-DR, CD38 or CD57, and stages of liver disease. This is in contrast to other chronic infections with viruses such as HIV [19,31] or HCMV [16] infections, where changes in these phenotypic markers have been found to correlate with disease progression.…”

Section: Discussionsupporting

confidence: 93%

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Composition of peripheral blood lymphocyte populations during different stages of chronic infection with hepatitis B virus

Sing

Butterworth

Chen

et al. 1998

Journal of Viral Hepatitis

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To characterize the immunological populations associated with different stages of chronic infection with hepatitis B virus (HBV), we performed flow cytometric analyses on the peripheral blood leucocytes of 29 patients with various forms of chronic hepatitis B. The clinical spectrum of the patients ranged from asymptomatic infections, in the presence of high virus production, to intermittent or recurrent exacerbations of liver injury alternating with relatively normal liver function. Patients with partial resolution of disease who experienced an initial acute flare followed by prolonged seroconversion showed decreased percentages of CD3+ cells during the seroconversion phase when levels of serum alanine transferase (ALT) had normalized. These CD3+ cells were predominantly CD4+ cells bearing the alpha beta+ T-cell receptor (TCR). In addition, we saw an increase in CD4+ and CD8+ cells bearing the gamma delta TCR in those patients who had seroconverted. No significant differences were seen between any of the groups with respect to percentage of cells with a naive (CD45RA) or memory (CD45RO) phenotype, or of cells displaying the activation markers CD38, HLA-DR or CD57. Longitudinal analyses of 15 patients failed to show any consistent pattern of changes in the immunophenotypic profile during acute flares and their resolution. Our results indicate that the turnover of circulating T lymphocytes during the apparent quiescent phase of chronic infections is higher than that during acute exacerbations, suggesting an active immunosurveillance role of T-cell subpopulations in maintaining low virus levels during seroconversion.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 93%

Composition of peripheral blood lymphocyte populations during different stages of chronic infection with hepatitis B virus

Sing

Butterworth

Chen

et al. 1998

Journal of Viral Hepatitis

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“…On the other hand, we observed apparent hepatitis in mice injected with PBMCs donated from an individual who had recently recovered from severe acute hepatitis. Furthermore, we detected HBV-specific CTLs in liverinfiltrating cells, which are thought to be necessary in acute liver inflammation (34)(35)(36)(37), as well as memory T cells (38). As we confirmed that depletion of CD8-positive T cells resulted in no occurrence of hepatitis (Fig.…”

Section: Discussionsupporting

confidence: 71%

Human Cytotoxic T Lymphocyte-Mediated Acute Liver Failure and Rescue by Immunoglobulin in Human Hepatocyte Transplant TK-NOG Mice

Uchida

Hiraga

Imamura

et al. 2015

J Virol

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Hepatitis B virus (HBV)-specific cytotoxic T lymphocytes (CTLs) are critical in eliminating infection. We developed an animal model in which HBV-infected human hepatocytes are targeted by HBV-specific CTLs. After HBV inoculation in human hepatocyte-transplanted herpes simplex virus type-1 thymidine kinase-NOG mice, human peripheral blood mononuclear cells (PBMCs) were administered, and albumin, HBV DNA, alanine aminotransferase (ALT), and cytokine levels were analyzed. Histopathological and flow-cytometric analysis of infiltrating human immune cells were performed, and the efficacy of CTL-associated antigen-4 immunoglobulin (CTLA4Ig) against liver damage was evaluated. PBMC treatment resulted in massive hepatocyte damage with elevation of ALT, granzyme A, and gamma interferon and decrease in albumin and HBV DNA. The number of liver-infiltrating human lymphocytes and CD8-positive cells was significantly higher in HBV-infected mice. HBV-specific CTLs were detected by core and polymerase peptide-major histocompatibility complex-tetramer, and the population of regulatory T cells was significantly decreased in HBV-infected mice. Serum hepatitis B surface (HBs) antigen became negative, and HBs antibody appeared. CTLA4Ig treatment strongly inhibited infiltration of mononuclear cells. CTLA4Ig treatment will be used to treat patients who develop severe acute hepatitis B to prevent liver transplantation or lethality. This animal model is useful for virological and immunological analysis of HBV infection and to develop new therapies for severe acute hepatitis B. IMPORTANCEWithout liver transplantation, some HBV-infected patients will die from severe liver damage due to acute overreaction of the immune system. No effective treatment exists, due in part to the lack of a suitable animal model. An animal model is necessary to investigate the mechanism of hepatitis and to develop therapeutic strategies to prevent acute liver failure in HBV infection. We developed an animal model in which HBV-infected human hepatocytes are targeted by human HBV-specific CTLs. In this model, HBV-infected human hepatocytes were transplanted into severely immunodeficient NOG mice in order to reconstruct elements of the human immune system. Using this model, we found that CTL-associated antigen-4 immunoglobulin was able to suppress damage to HBV-infected hepatocytes, suggesting an approach to treatment. This animal model is useful for virological and immunological analysis of HBV infection and to develop new therapies for severe acute hepatitis B.

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“…In the peripheral lymphocytes of acute hepatitis patients, a similar increase in CD45RO + T cells was observed, whereas such an increase in CD45RO + T cells was not observed in peripheral T cells obtained from patients with chronic hepatitis B. 15 …”

Section: Discussionmentioning

confidence: 71%

Increase in CD95 (Fas/APO‐1)‐positive CD4⁺ and CD8⁺ T cells in peripheral blood derived from patients with autoimmune hepatitis or chronic hepatitis C with autoimmune phenomena

Ogawa

Sakaguchi

Takaki

et al. 2000

J of Gastro and Hepatol

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These results indicate that an increase in CD4+ T cells expressing CD45RO and CD95 marks an important subset of AIH and CH-C(AI) patients. These expanded CD95+ CD45RO+ primed T cells most likely reflect a continuous antigen-specific or non-specific activation of T lymphocytes, and/or the persistent presence of activated lymphocytes as a consequence of abnormalities in the peripheral deletion of activated lymphocytes. These persistently activated lymphocytes might play a role in the induction of autoimmunity in AIH and CH-C(AI).

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Increased frequency of CD8+ CD45R0+ memory T lymphocytes in acute hepatitis B virus infection

Cited by 19 publications

References 12 publications

Composition of peripheral blood lymphocyte populations during different stages of chronic infection with hepatitis B virus

Composition of peripheral blood lymphocyte populations during different stages of chronic infection with hepatitis B virus

Human Cytotoxic T Lymphocyte-Mediated Acute Liver Failure and Rescue by Immunoglobulin in Human Hepatocyte Transplant TK-NOG Mice

Increase in CD95 (Fas/APO‐1)‐positive CD4⁺ and CD8⁺ T cells in peripheral blood derived from patients with autoimmune hepatitis or chronic hepatitis C with autoimmune phenomena

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Increased frequency of CD8+ CD45R0+ memory T lymphocytes in acute hepatitis B virus infection

Cited by 19 publications

References 12 publications

Composition of peripheral blood lymphocyte populations during different stages of chronic infection with hepatitis B virus

Composition of peripheral blood lymphocyte populations during different stages of chronic infection with hepatitis B virus

Human Cytotoxic T Lymphocyte-Mediated Acute Liver Failure and Rescue by Immunoglobulin in Human Hepatocyte Transplant TK-NOG Mice

Increase in CD95 (Fas/APO‐1)‐positive CD4+ and CD8+ T cells in peripheral blood derived from patients with autoimmune hepatitis or chronic hepatitis C with autoimmune phenomena

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Increase in CD95 (Fas/APO‐1)‐positive CD4⁺ and CD8⁺ T cells in peripheral blood derived from patients with autoimmune hepatitis or chronic hepatitis C with autoimmune phenomena