TY - JOUR
T1 - Promotion of Corneal Allograft Survival by the Induction of Oxidative Macrophages
AU - Yamada, Jun
AU - Maruyama, Kazuichi
AU - Sano, Yoichiro
AU - Kinoshita, Shigeru
AU - Murata, Yukie
AU - Hamuro, Junji
PY - 2004/2
Y1 - 2004/2
N2 - PURPOSE. A Th1-type immune response was detected in allo-transplanted, rejected corneas. Because the intracellular thiol redox status of antigen-presenting cells (APCs) reportedly regulates the Th1/Th2 balance through distinctive cytokine production by APCs, this study was conducted to investigate the effect of the intracellular thiol redox status of macrophages (Mps) on corneal allograft survival. METHODS. N,N′-diacetyl-L-cystine dimethylester (NACOMe)2 was injected intraperitoneally into BALB/c (H-2d) mice to induce Mps with a low intracellular glutathione content (icGSH). Corneal grafts from C57BL/10 (H-2b), B10.D2 (H-2d), and DBA/2 (H-2d) donor mice were placed on neovascularized BALB/c graft beds for assessment. B10.D2-grafted recipients were evaluated for donor-specific delayed-type hypersensitivity (DTH), and the cytokines produced by their lymphocytes were examined (IFN-γ, IL-4, and IL-10). In other experiments, naïve BALB/c mice, injected intravenously with Mps of low icGSH content, received B10.D2 corneal grafts. RESULTS. In. (NACOMe) 2-treated mice, 13 of 20 B10.D2 grafts and 6 of 10 DBA/2 grafts survived indefinitely. No grafts survived in the control mice (P < 0.0001). (NACOMe)2 treatment did not enhance C57BL/10 graft survival. At 2 weeks after B10.D2 grafting, control mice exhibited DTH, but (NACOMe) 2-treated mice did not (P < 0.01). Lymphocytes from (NACOMe) 2-treated mice did not respond to donor splenocytes. Those of control mice showed Th1-type cytokine secretion. The intravenous transfer of peritoneal Mps from (NA-COMe)2-treated mice prolonged corneal allograft survival (P < 0.003). CONCLUSIONS. The observed enhanced graft acceptance may be due to the suppression of alloantigen-induced Th1 polarization through the induction of Mps with reduced icGSH levels.
AB - PURPOSE. A Th1-type immune response was detected in allo-transplanted, rejected corneas. Because the intracellular thiol redox status of antigen-presenting cells (APCs) reportedly regulates the Th1/Th2 balance through distinctive cytokine production by APCs, this study was conducted to investigate the effect of the intracellular thiol redox status of macrophages (Mps) on corneal allograft survival. METHODS. N,N′-diacetyl-L-cystine dimethylester (NACOMe)2 was injected intraperitoneally into BALB/c (H-2d) mice to induce Mps with a low intracellular glutathione content (icGSH). Corneal grafts from C57BL/10 (H-2b), B10.D2 (H-2d), and DBA/2 (H-2d) donor mice were placed on neovascularized BALB/c graft beds for assessment. B10.D2-grafted recipients were evaluated for donor-specific delayed-type hypersensitivity (DTH), and the cytokines produced by their lymphocytes were examined (IFN-γ, IL-4, and IL-10). In other experiments, naïve BALB/c mice, injected intravenously with Mps of low icGSH content, received B10.D2 corneal grafts. RESULTS. In. (NACOMe) 2-treated mice, 13 of 20 B10.D2 grafts and 6 of 10 DBA/2 grafts survived indefinitely. No grafts survived in the control mice (P < 0.0001). (NACOMe)2 treatment did not enhance C57BL/10 graft survival. At 2 weeks after B10.D2 grafting, control mice exhibited DTH, but (NACOMe) 2-treated mice did not (P < 0.01). Lymphocytes from (NACOMe) 2-treated mice did not respond to donor splenocytes. Those of control mice showed Th1-type cytokine secretion. The intravenous transfer of peritoneal Mps from (NA-COMe)2-treated mice prolonged corneal allograft survival (P < 0.003). CONCLUSIONS. The observed enhanced graft acceptance may be due to the suppression of alloantigen-induced Th1 polarization through the induction of Mps with reduced icGSH levels.
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U2 - 10.1167/iovs.03-0939
DO - 10.1167/iovs.03-0939
M3 - Article
C2 - 14744884
AN - SCOPUS:0942265589
SN - 0146-0404
VL - 45
SP - 448
EP - 454
JO - Investigative Ophthalmology
JF - Investigative Ophthalmology
IS - 2
ER -