Intact LFA-1 deactivation promotes T-cell activation and rejection of cardiac allograft.
Leucocyte function-associated antigen-1 (LFA-1) is known to be involved in immune reactions leading to allograft rejection. The role of deactivating LFA-1 in this context has not been investigated yet, although it is accepted that regulating LFA-1 activity is essential for T-cell function. Expressing LFA-1 locked in an active state in mice (LFA-1(d/d)) allowed us to investigate the in vivo function of LFA-1 deactivation for allograft rejection in a model of heterotopic cardiac transplantation. We provide in vivo evidence that regulating LFA-1 activity from an active to an inactive state controls antigen-specific priming and proliferation of T cells in response to allogeneic stimuli. Consequently, defective LFA-1 deactivation significantly prolonged cardiac allograft survival. Furthermore, reduced numbers of alloantigen-specific T cells and non-allo-specific innate immune cells within allografts of LFA-1(d/d) recipients indicate that expression of active LFA-1 impairs inflammatory responses involving all major leucocyte subpopulations. Taken together, our in vivo data suggest that LFA-1 deactivation is important for the formation of inflammatory lesions and rejection of cardiac allografts. Thus, the dynamic regulation of LFA-1 activity, rather than the mere presence of LFA-1, appears to contribute to the control of immune reactions inducing allogeneic transplant rejection.
Hüser
Norbert
N
Department of Surgery, Technische Universität München, Ismaninger Strasse 22, 81675 Munich, Germany.
Fasan
Annette
A
Semmrich
Monika
M
Schmidbauer
Patricia
P
Holzmann
Bernhard
B
Laschinger
Melanie
M
D000818:Animals; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D049109:Cell Proliferation; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D006085:Graft Survival / Q000235:genetics / Q000276:immunology; D016027:Heart Transplantation; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
D016169:Lymphocyte Function-Associated Antigen-1