J2 prolongs the corneal allograft survival through inhibition of the CD4+ T cell-mediated response in vivo.
In our previous report, we described a novel non-peptidic organic ligand of CD4 D1, designated J2, as a potential inhibitor of CD4 D1 and thus CD4-dependent T cell responses in vitro. In this work, we further used a murine model of corneal allograft rejection to determine its in vivo immunosuppressive activities. To mimic the situation in high-risk human eyes, the recipient mice corneas were all induced by intrastromal sutures to serve as neovascularized graft beds. J2 was administrated by mouth 3 h before transplantation and thereafter on consecutive 12 days. The results showed that J2 could significantly prolong the median survival time of the corneal allografts, compared to the untreated control group. And the subsequent functional assays, including T cell phenotype analysis, delayed-type hypersensitivity (DTH) and enzyme-linked immunospot (ELISPOT) assays revealed that the immunosuppressive activity of J2 was associated with its inhibitory effects on the CD4(+) T cells and these cells-mediated responses. All these results suggest that J2 is a potential lead for the development of new immunosuppressive agents to prevent the corneal allograft rejection.
Xiao
He
H
Department of Molecular Immunology, Institute of Basic Medical Sciences, 100850, Beijing, China.
Zhang
Han
H
Yu
Zu-Yin
ZY
Zhang
Lei
L
Yu
Ming
M
Huang
Yi-Fei
YF
Li
Song
S
Shen
Bei-Fen
BF
Li
Yan
Y
D000178:Acrylamides / Q000494:pharmacology*; D000818:Animals; D015704:CD4 Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D016039:Corneal Transplantation / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D005260:Female; D006085:Graft Survival / Q000187:drug effects* / Q000276:immunology; D006968:Hypersensitivity, Delayed / Q000276:immunology / Q000517:prevention & control; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology*; D008024:Ligands; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D023001:Transplantation Tolerance / Q000187:drug effects / Q000276:immunology; D014184:Transplantation, Homologous
D000178:Acrylamides; D015704:CD4 Antigens; D016207:Cytokines; D007166:Immunosuppressive Agents; D007211:Indoles; D008024:Ligands; C517552:N-(6-methylamino-3-nitrophenyl)-3-(3-indolyl)acrylamide