Identification of a unique population of tissue-memory CD4+ T cells in the airways after influenza infection that is dependent on the integrin VLA-1.
During the immune response to influenza infection, activated T cells are distributed to both lymphoid and extralymphoid tissues, including the infected airways where direct recognition of viral Ag-bearing cells takes place. The collagen-binding alpha(1)beta(1) integrin VLA-1 is essential for the development of memory CD8(+) T cells in the airways, and although expressed by some CD4(+) T cells, its significance has not been demonstrated. We investigated the role of VLA-1 on virus-specific CD4(+) T cells during and after primary or secondary influenza infection of mice. The proportion of CD4(+) cells expressing CD49a (alpha(1) integrin) was low in all tissues sampled during primary infection but increased in the airways after viral clearance. Furthermore, during the first 24 h of a secondary influenza challenge, the majority of IFN-gamma-secreting effector CD4(+) T cells from the airways was in the CD49a(+) population. Airway CD49a(+)CD4(+) cells also expressed reduced markers of apoptosis compared with CD49a(-) cells, and fewer memory or effector CD4(+) cells could be recovered from airways of alpha(1)(-/-) mice, although lymphoid tissues appeared unaffected. These data suggest VLA-1 expression defines a population of tissue memory CD4(+) T cells that act as rapid effectors upon reinfection, and VLA-1 expression is integral to their accumulation in the airways.
Chapman
Timothy J
TJ
Department of Microbiology and Immunology, David H Smith Center for Vaccine Biology and Immunology, Aab Institute of Biomedical Sciences, University of Rochester, Rochester, NY 14642, USA.
Topham
David J
DJ
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002469:Cell Separation; D005434:Flow Cytometry; D007156:Immunologic Memory; D009980:Influenza A virus / Q000276:immunology; D039222:Integrin alpha1beta1 / Q000276:immunology*; D008168:Lung / Q000276:immunology* / Q000821:virology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D039222:Integrin alpha1beta1