The alpha1beta1 integrin and TNF receptor II protect airway CD8+ effector T cells from apoptosis during influenza infection

J Immunol. 2007 Oct 15;179(8):5054-63. doi: 10.4049/jimmunol.179.8.5054.

Abstract

Primary viral infections of the lung induce potent effector CD8 T cell responses. To function in the influenza-infected airways, CD8 T cells must be able to resist cell death. The majority of the CD8 T cells in the airways and lung parenchyma expressed CD49a, the alpha-chain of the type IV collagen receptor VLA-1, and these cells were highly activated, producing both IFN-gamma and TNF-alpha. In the airways, where type IV collagen is abundant, but not the spleen, the CD49a(+) CD8 cells had reduced proportions of annexin V and caspase 8, and >80% expressed the TNF-alpha receptor II, while Fas, TNFR-I, and CD27 expression were similar to CD49a(-) cells. Furthermore, the CD49a(+), but not CD49a(-), CD8 T cells from the airways were resistant to active induction of apoptosis in the presence of type IV collagen and TNF-alpha in vitro. We propose that TNFR-II and the VLA-1 synergize to protect effector CD8 T cells in the infected airways from apoptosis during the acute infection.

Publication types

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

MeSH terms

  • Animals
  • Apoptosis / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / pathology*
  • Cell Separation
  • Female
  • Immunophenotyping
  • Influenza A Virus, H3N2 Subtype / immunology
  • Integrin alpha1 / biosynthesis
  • Integrin alpha1 / metabolism
  • Integrin alpha1beta1 / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Orthomyxoviridae Infections / immunology*
  • Orthomyxoviridae Infections / metabolism*
  • Orthomyxoviridae Infections / pathology
  • Receptors, Tumor Necrosis Factor, Type II / physiology*
  • Respiratory Mucosa / immunology*
  • Respiratory Mucosa / metabolism
  • Respiratory Mucosa / pathology
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocyte Subsets / pathology

Substances

  • Integrin alpha1
  • Integrin alpha1beta1
  • Receptors, Tumor Necrosis Factor, Type II