Pivotal role of VLA-1 in CD8 T cell retention & survival

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DESCRIPTION (provided by applicant): Virus-specific T cell memory is important to protect the host from secondary exposure to the same or related viruses. The localization of these memory T cells and their activation status determines the efficiency of the secondary immune response. A substantial extralymphoid memory population that is functionally distinct from the lymphoid memory cells has recently been described. The mechanism by which these memory T cells can be retained in non-lymphoid tissue is not known. We present preliminary data that show virus specific CD8+ T cells rapidly acquire expression of the integrin VLA-1 during influenza infection. VLA-1 is the receptor for Type I and IV collagen. VLA-1+ flu-specific CD8 T cells show resistance to apoptosis and selectively accumulate in the lung and other non-lymphoid tissues during resolution of the infection. Postimmune inhibition of VLA-1+ reduces the number of flu-specific T cells in the lung and compromises secondary immunity. From this we have formed the hypothesis that binding of VLA-1+ CD8 T cells to Types I and IV collagen promotes retention and survival of memory T cells within non-lymphoid tissues. These CD8+/VLA - 1+ CD8 T cells may be preferentially retained in non-lymphoid tissues to provide a first line of defense against secondary infection. The experiments in this proposal will establish the role of VLA-1 in the retention and survival of virus-specific CD8 T cells in tissue via collagen-binding. We will also test the prediction that the VLA-1+ memory T cells are functionally distinct and important for secondary immune protection.