The alpha1beta1 integrin and TNF receptor II protect airway CD8+ effector T cells from apoptosis during influenza infection.
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.
Richter
Martin V
MV
Department of Microbiology and Immunology, University of Rochester, Rochester, NY 14642, USA.
Topham
David J
DJ
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D002469:Cell Separation; D005260:Female; D016130:Immunophenotyping; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology; D039423:Integrin alpha1 / Q000096:biosynthesis / Q000378:metabolism; D039222:Integrin alpha1beta1 / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000502:physiology*; D020545:Respiratory Mucosa / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000473:pathology
D039423:Integrin alpha1; D039222:Integrin alpha1beta1; D047889:Receptors, Tumor Necrosis Factor, Type II