Open Access

CTLA‑4 interferes with the HBV‑specific T cell immune response (Review)

  • Authors:
    • Hui Cao
    • Ruiwen Zhang
    • Wei Zhang
  • View Affiliations

  • Published online on: May 17, 2018     https://doi.org/10.3892/ijmm.2018.3688
  • Pages: 703-712
  • Copyright: © Cao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Hepatitis B virus (HBV) infection is a major cause of hepatic inflammation. Successful HBV clearance in patients is associated with sustained viral control by effector T cells. Compared with acute hepatitis B, chronic HBV infection is associated with the depletion of T cells, resulting in weak or absent virus‑specific T cells reactivity, which is described as ‘exhaustion’. This exhaustion is characterized by impaired cytokine production and sustained expression of multiple coinhibitory molecules. Cytotoxic T lymphocyte‑associated antigen‑4 (CTLA‑4) is one of many coinhibitory molecules that can attenuate T cell activation by inhibiting costimulation and transmitting inhibitory signals to T cells. Persistent HBV infection results in the upregulation of CTLA‑4 on hepatic CD8+ T cells. This prompts CD8+ T cell apoptosis, and the activation of cytotoxic T lymphocytes is blocked. Similar to CD8+ T cells, CD4+ T helper (Th) cell proliferation is hindered following CTLA‑4 upregulation. In addition, the differentiation of CD4+ Th is polarized toward the Th2/peripherally‑inducible T regulatory cell types, increasing the levels of anti‑inflammatory cytokines. Conversely, the activation of proinflammatory cells (Th1 and follicular helper T) is blocked, and the levels of proinflammatory cytokines decline. This review summarizes the current literature relevant to T cell exhaustion in patients with HBV‑related chronic hepatitis, and discusses the roles of CTLA‑4 in T cell exhaustion.
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August-2018
Volume 42 Issue 2

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Cao H, Zhang R and Zhang W: CTLA‑4 interferes with the HBV‑specific T cell immune response (Review) . Int J Mol Med 42: 703-712, 2018
APA
Cao, H., Zhang, R., & Zhang, W. (2018). CTLA‑4 interferes with the HBV‑specific T cell immune response (Review) . International Journal of Molecular Medicine, 42, 703-712. https://doi.org/10.3892/ijmm.2018.3688
MLA
Cao, H., Zhang, R., Zhang, W."CTLA‑4 interferes with the HBV‑specific T cell immune response (Review) ". International Journal of Molecular Medicine 42.2 (2018): 703-712.
Chicago
Cao, H., Zhang, R., Zhang, W."CTLA‑4 interferes with the HBV‑specific T cell immune response (Review) ". International Journal of Molecular Medicine 42, no. 2 (2018): 703-712. https://doi.org/10.3892/ijmm.2018.3688