Expression and functional importance of collagen-binding integrins, alpha 1 beta 1 and alpha 2 beta 1, on virus-activated T cells.
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.
Andreasen
Susanne Ø
SØ
Institute of Medical Microbiology and Immunology, Panum Institute, Copenhagen, Denmark. Biogen, Cambridge, MA 02142, USA.
Thomsen
Allan R
AR
Koteliansky
Victor E
VE
Novobrantseva
Tatiana I
TI
Sprague
Andrew G
AG
de Fougerolles
Antonin R
AR
Christensen
Jan P
JP
D019264:Adoptive Transfer; D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D003094:Collagen / Q000378:metabolism*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D006614:Hindlimb; D016130:Immunophenotyping; D007279:Injections, Subcutaneous; D039222:Integrin alpha1beta1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology*; D038982:Integrin alpha2beta1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000378:metabolism / Q000502:physiology*; D007700:Kinetics; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D008216:Lymphocytic Choriomeningitis / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011485:Protein Binding; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000637:transplantation; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000821:virology*
D000956:Antigens, Viral; D018984:Epitopes, T-Lymphocyte; D039222:Integrin alpha1beta1; D038982:Integrin alpha2beta1; D003094:Collagen