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Expression and Functional Importance of Collagen-Binding Integrins, ₁₁ and ₂₁, on Virus-Activated T Cells ¹

Susanne Ø. Andreasen^*, Allan R. Thomsen^*, Victor E. Koteliansky, Tatiana I. Novobrantseva, Andrew G. Sprague, Antonin R. de Fougerolles^2, and Jan P. Christensen^2,3,*

^* Institute of Medical Microbiology and Immunology, Panum Institute, Copenhagen, Denmark; and Biogen, Cambridge, MA 02142

Adhesive interactions are crucial to cell migration into inflammatory sites. Using murine lymphocytic choriomeningitis virus as an Ag model system, we have investigated expression and function of collagen-binding integrins, ₁₁ and ₂₁, on activated and memory T cells. Using this system and MHC tetramers to define Ag-specific T cells, we demonstrate that contrary to being VLAs, expression of ₁₁ and ₂₁ can be rapidly induced on acutely activated T cells, that expression of ₁₁ remains elevated on memory T cells, and that expression of ₁₁ parallels that of viral-specific effector CD8⁺ T cells (defined by tetramer and IFN- staining). In an adoptive transfer model, mAb-mediated blockade of these integrins on activated effector and memory T cells inhibited Ag-specific delayed-type hypersensitivity responses; similar decreased responses were seen upon transfer of ₁-deficient activated/memory T cells. Thus, expression of ₁₁ and ₂₁ integrins on activated T cells is directly functionally important for generation of inflammatory responses within tissues. Finally, the inhibitory effect of ₁₁ blockade on the delayed-type hypersensitivity response could be bypassed by direct injection of Ag-specific T cells to inflammatory sites, demonstrating for the first time in vivo that collagen-binding integrins are involved in leukocyte migration into tissues.

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