Expression and functional importance of collagen-binding integrins, alpha 1 beta 1 and alpha 2 beta 1, on virus-activated T cells
Autor: | Susanne Ø, Andreasen, Allan R, Thomsen, Victor E, Koteliansky, Tatiana I, Novobrantseva, Andrew G, Sprague, Antonin R, de Fougerolles, Jan P, Christensen |
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Rok vydání: | 2003 |
Předmět: |
Mice
Knockout Mice Inbred BALB C Injections Subcutaneous Epitopes T-Lymphocyte CD8-Positive T-Lymphocytes Lymphocytic Choriomeningitis Lymphocyte Activation Adoptive Transfer Hindlimb Immunophenotyping Integrin alpha1beta1 Mice Inbred C57BL Kinetics Mice T-Lymphocyte Subsets Animals Lymphocytic choriomeningitis virus Female Collagen Integrin alpha2beta1 Antigens Viral Spleen Protein Binding |
Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 171(6) |
ISSN: | 0022-1767 |
Popis: | 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, alpha(1)beta(1) and alpha(2)beta(1), 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 alpha(1)beta(1) and alpha(2)beta(1) can be rapidly induced on acutely activated T cells, that expression of alpha(1)beta(1) remains elevated on memory T cells, and that expression of alpha(1)beta(1) parallels that of viral-specific effector CD8(+) T cells (defined by tetramer and IFN-gamma 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 alpha(1)-deficient activated/memory T cells. Thus, expression of alpha(1)beta(1) and alpha(2)beta(1) integrins on activated T cells is directly functionally important for generation of inflammatory responses within tissues. Finally, the inhibitory effect of alpha(1)beta(1) 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. |
Databáze: | OpenAIRE |
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