Programmed death 1 regulates development of central memory CD8 T cells after acute viral infection

J Immunol. 2011 Jun 1;186(11):6280-6. doi: 10.4049/jimmunol.1003870. Epub 2011 Apr 27.


The T cell response possesses a number of inhibitory receptors to regulate the extent of the antiviral response and prevent immune pathology. These receptors are generally transiently upregulated during an effector response and then downregulated during memory. Some inhibitory receptors, such as programmed death 1 (PD-1) and LAG-3, were shown to be aberrantly upregulated during memory to chronic lymphocytic choriomeningitis virus infection, limiting functional capabilities. However, little is known about the impact of inhibitory receptors on memory development during a normal CD8 T cell response to acute virus infection. Our previous data showed that PD-1 is aberrantly upregulated during a secondary response by memory CD8 T cells that were generated without CD4 T cell help. Therefore, we examined the role of PD-1 in memory differentiation during acute vaccinia virus infection in intact mice. In the absence of PD-1, the primary and memory CD8 T cell responses were enhanced. Moreover, there were distinct phenotypic and functional changes in the memory PD-1(-/-) CD8 T cells. Higher levels of CD62L, CD27, and CCR7 were detected; cells produced more IL-2 and made an enhanced secondary response. These changes indicate a skewing of the memory population toward the central memory phenotype in the absence of PD-1 signaling.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antigens, Surface / genetics
  • Antigens, Surface / immunology*
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Flow Cytometry
  • Host-Pathogen Interactions / immunology
  • Immunologic Memory / immunology*
  • Interferon-gamma / immunology
  • Interferon-gamma / metabolism
  • Interleukin-2 / immunology
  • Interleukin-2 / metabolism
  • L-Selectin / immunology
  • L-Selectin / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Programmed Cell Death 1 Receptor
  • Receptors, CCR7 / immunology
  • Receptors, CCR7 / metabolism
  • Signal Transduction / genetics
  • Signal Transduction / immunology
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / immunology
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / metabolism
  • Vaccinia / genetics
  • Vaccinia / immunology*
  • Vaccinia / virology
  • Vaccinia virus / immunology
  • Vaccinia virus / physiology


  • Antigens, Surface
  • Apoptosis Regulatory Proteins
  • Ccr7 protein, mouse
  • Interleukin-2
  • Pdcd1 protein, mouse
  • Programmed Cell Death 1 Receptor
  • Receptors, CCR7
  • Tumor Necrosis Factor Receptor Superfamily, Member 7
  • L-Selectin
  • Interferon-gamma