Dispensable role for 4-1BB and 4-1BBL in development of vaccinia virus-specific CD8 T cells

Immunol Lett. 2012 Jan 30;141(2):220-6. doi: 10.1016/j.imlet.2011.10.008. Epub 2011 Oct 20.

Abstract

CD8 T cells are strongly induced in response to certain strains of vaccinia virus (VACV) and the generation of this population is tightly regulated by two Tumor Necrosis Factor (TNF)/TNFR superfamily members, OX40 (CD134) and CD27. In this study, we examined the role of another member of the TNFR superfamily, 4-1BB (CD137, TNFRSF9), and its ligand (4-1BBL, CD137L, TNFSF9), that have been described to control the generation of memory CD8 T cell populations elicited by other viruses such as influenza. Expression of 4-1BB and 4-1BBL was observed in wild-type mice during the primary infection, but we found that both 4-1BB and 4-1BBL deficient mice generated normal numbers of VACV-specific effector CD8 T cells that produced IFN-γ and TNF. Additionally, CD8 T cells deficient in 4-1BB were able to expand and persist comparably to wild-type T cells in response to VACV infection. Furthermore, the knockout mice also showed no defect in development of VACV-specific CD8 memory T cell populations. Lastly, showing alternate control mechanisms were not active in the gene-deficient environments that masked any activity, blocking 4-1BB/4-1BBL interactions using neutralizing antibody also had no effect on the number of VACV-specific memory CD8 T cells induced. Thus, our data demonstrate that 4-1BB and 4-1BBL do not play a strong or dominant role in driving the generation of high frequencies of VACV-specific CD8 T cells.

Publication types

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

MeSH terms

  • 4-1BB Ligand / antagonists & inhibitors
  • 4-1BB Ligand / genetics
  • 4-1BB Ligand / immunology
  • 4-1BB Ligand / metabolism*
  • Animals
  • Antibodies, Blocking / pharmacology
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism*
  • CD8-Positive T-Lymphocytes / pathology
  • CD8-Positive T-Lymphocytes / virology
  • Cells, Cultured
  • Immunologic Memory / drug effects
  • Immunologic Memory / genetics
  • Interferon-gamma / metabolism
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Tumor Necrosis Factor Receptor Superfamily, Member 9 / antagonists & inhibitors
  • Tumor Necrosis Factor Receptor Superfamily, Member 9 / genetics
  • Tumor Necrosis Factor Receptor Superfamily, Member 9 / immunology
  • Tumor Necrosis Factor Receptor Superfamily, Member 9 / metabolism*
  • Tumor Necrosis Factor-alpha / metabolism
  • Vaccinia / genetics
  • Vaccinia / immunology*
  • Vaccinia virus / immunology*
  • Vaccinia virus / pathogenicity

Substances

  • 4-1BB Ligand
  • Antibodies, Blocking
  • Tumor Necrosis Factor Receptor Superfamily, Member 9
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma