Cutting edge: programmed death-1 up-regulation is involved in the attrition of cytomegalovirus-specific CD8+ T cells in acute self-limited hepatitis B virus infection

J Immunol. 2008 Sep 15;181(6):3741-4. doi: 10.4049/jimmunol.181.6.3741.

Abstract

Attrition of heterologous virus-specific CD8(+) T cells has been demonstrated in murine viral infection; however, little is known regarding this phenomenon in human viral infections. In this study, we observed that CMV-specific CD8(+) T cells displayed numerical decline and functional impairment in the early phase of acute infection, whereas programmed death-1 (PD-1) expression was significantly up-regulated by these CMV-specific CD8(+) T cells. This early PD-1 up-regulation was found to be closely associated with the increased apoptotic sensitivity of CMV-specific CD8(+) T cells. The in vitro addition of anti-PD-1 further enhanced the spontaneous apoptosis of CMV-specific CD8(+) T cells; however, blockade of the PD-1-mediated pathway with anti-PD-L1 significantly restored the CMV-specific CD8(+) T cell proliferation and IFN-gamma production. Thus, PD-1 plays a crucial role in the attrition of CMV-specific CD8(+) T cells in acute hepatitis B virus infection, which in turn, influences the preexisting homeostatic virus-specific CD8(+) T cell pool.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adult
  • Antigens, CD / biosynthesis*
  • Antigens, CD / physiology
  • Apoptosis / immunology
  • Apoptosis Regulatory Proteins / biosynthesis*
  • Apoptosis Regulatory Proteins / physiology
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / pathology
  • CD8-Positive T-Lymphocytes / virology*
  • Cytomegalovirus / immunology*
  • Cytomegalovirus Infections / immunology
  • Cytomegalovirus Infections / metabolism
  • Cytomegalovirus Infections / pathology
  • Epitopes, T-Lymphocyte / immunology*
  • Female
  • Hepatitis B / immunology*
  • Hepatitis B / metabolism*
  • Hepatitis B / pathology
  • Homeostasis / immunology
  • Humans
  • Lymphocyte Count
  • Male
  • Programmed Cell Death 1 Receptor
  • Up-Regulation / immunology*

Substances

  • Antigens, CD
  • Apoptosis Regulatory Proteins
  • Epitopes, T-Lymphocyte
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor