Absence of allograft ICAM-1 attenuates alloantigen-specific T cell priming, but not primed T cell trafficking into the graft, to mediate acute rejection.
The expression and function of ICAM-1 are critical components in the initiation and elicitation of many T cell-mediated responses. Whether ICAM-1 expression is required on the T cells or on the APC during T cell priming remains unclear. To address this issue in alloantigen-specific T cell activation, the priming and function of T cells in response to heart allografts from MHC-mismatched wild-type vs ICAM-1(-/-) donors were tested. Wild-type C57BL/6 (H-2(b)) heart allografts were rejected by A/J (H-2(a)) recipients on days 7-9, whereas B6.ICAM-1(-/-) allografts survived until days 18-23 post-transplant. On day 7 post-transplant, infiltrating macrophages and CD4(+) and CD8(+) T cells in the ICAM-1(-/-) allografts were 20-30% those observed in the wild-type allografts. ELISPOT analyses indicated that the number of alloantigen-specific T cells producing IFN-gamma from recipients of ICAM-1-deficient grafts was 60% lower than that from recipients of wild-type allografts. On day 16 post-transplant, these numbers did not markedly increase in ICAM-1-deficient allograft recipients. Consistent with the reduced priming of alloreactive T cells, isolated dendritic cells from ICAM-1(-/-) mice stimulated allogeneic T cell proliferation poorly compared with wild-type dendritic cells. When A/J mice were primed with wild-type dendritic cells and then received wild-type or ICAM-1-deficient heart allografts 3 days later, the primed recipients rejected the wild-type and ICAM-1(-/-) allografts on days 5-6 post-transplant. These results indicate that optimal priming of alloreactive T cells requires allograft expression of ICAM-1, but, once primed, recipient T cell infiltration into the allograft is independent of graft ICAM-1 expression.
Zhang
Qi-Wei
QW
Department of Immunology, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
Kish
Danielle D
DD
Fairchild
Robert L
RL
D000208:Acute Disease; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D001854:Bone Marrow Cells / Q000276:immunology; D016026:Bone Marrow Transplantation; D002465:Cell Movement / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology / Q000637:transplantation; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D006085:Graft Survival / Q000235:genetics / Q000276:immunology; D016027:Heart Transplantation / Q000276:immunology* / Q000473:pathology; D007114:Immunization; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D007519:Isoantigens / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed / Q000379:methods; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013045:Species Specificity; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000473:pathology; D016042:Transplantation, Heterotopic / Q000276:immunology / Q000473:pathology
D018984:Epitopes, T-Lymphocyte; D007519:Isoantigens; D018799:Intercellular Adhesion Molecule-1