ADAP deficiency combined with costimulation blockade synergistically protects intestinal allografts.
Adhesion and degranulation promoting adapter protein (ADAP) plays an important role in T cell activation. ADAP deficiency was recently found to prolong heart graft survival in mice. We investigated the role of ADAP in intestinal transplantation and the synergistic effect of ADAP deficiency and Costimulation blockade (CB). T cell proliferation and cytotoxic T lymphocyte (CTL) activity were determined. MHC mismatched intestinal allografts was transplanted heterotopically. Anti-CD40L antibody was applied to the recipient. Upon stimulation with allogenic dendritic cells (DC), ADAP-deficient (ADAP-/-) T cells displayed impaired proliferative responses compared with that of wild-type (WT) T cells. In contrast, the CTL activity in ADAP-/- mice was comparable with that of WT mice. Rejection of intestinal allografts was ameliorated, but not prevented in ADAP-/- mice. Although CB alone was not sufficient to mitigate the rejection, the combination of CB and ADAP deficiency profoundly inhibited rejection. This was accompanied by less infiltration and activation of host lymphocytes in the gut-associated lymphoid tissue of intestinal allografts. ADAP deficiency combined with CB protected the intestinal allografts synergistically. ADAP could be a novel target in the induction phase of the immune responses in organ transplantation.
Tian
Jiong
J
Kidney Disease Center, The 1st Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
Rodriguez-Barbosa
Jose-Ignacio
JI
Pabst
Oliver
O
Roemermann
Dorothee
D
Foerster
Reinhold
R
Beckmann
Jan
J
Hoffmann
Matthias W
MW
D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology*; D006085:Graft Survival / Q000276:immunology; D007422:Intestines / Q000473:pathology / Q000637:transplantation*; D019041:L-Selectin / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000502:physiology
D048868:Adaptor Proteins, Signal Transducing; C491468:Fyb protein, mouse; D019041:L-Selectin