Rejection of mouse cardiac allografts by costimulation in trans.
The activation of T cells by B7 costimulation in trans has been demonstrated in vitro, but the in vivo relevance is unknown. To study costimulation in trans of CD4(+) T cells in vivo, we performed cardiac transplants from B7-1/B7-2-deficient mice to recipients that do not express MHC class II molecules on peripheral APCs, but do have functional CD4(+) T cells (II(-)/4(+) mice). This model restricts the B7-dependent activation of CD4(+) T cells to costimulation in trans and excludes any contribution from indirect Ag presentation. We find that II(-)/4(+) recipients reject B7-deficient grafts as rapidly as wild-type grafts, suggesting that costimulation in trans can mediate rejection as potently as costimulation in cis. Treatment of II(-)/4(+) recipients of B7-deficient grafts with depleting Abs to CD4 or CD8 demonstrates that indirect Ag presentation to CD8(+) cells does not significantly contribute to rejection. This is the first demonstration that costimulation in trans can mediate an immune response in vivo and has important therapeutic implications.
Mandelbrot
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DA
Immunology Research Division, Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA. mandelbd@ummhc.org
Kishimoto
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K
Auchincloss
H
H
Sharpe
A H
AH
Sayegh
M H
MH
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D018122:B7-1 Antigen / Q000235:genetics / Q000276:immunology; D051940:B7-2 Antigen; D015704:CD4 Antigens / Q000096:biosynthesis / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D006084:Graft Rejection / Q000235:genetics* / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D008213:Lymphocyte Activation / Q000235:genetics*; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D014184:Transplantation, Homologous
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D015704:CD4 Antigens; C497965:Cd86 protein, mouse; D000949:Histocompatibility Antigens Class II; D008562:Membrane Glycoproteins