Induced liver allograft immunological tolerance in rats by intramuscular injection of recombinant adeno-associated virus-human cytotoxic T-lymphocyte-associated antigen-4 immunoglobulin (rAAV-hCTLA4Ig).
Induction of liver allograft immunological tolerance was performed in rats by intramuscular injection of recombinant adeno-associated virus-human cytotoxic T-lymphocyte-associated antigen-4 immunoglobulin (rAAV-hCTLA4Ig). Dark Agouti and Lewis rats were liver allograft donors and recipients, respectively, in four groups: (A) syngeneic control, (B) blank control, (C) rAAV-enhanced green fluorescent protein negative control, (D) rAAV-hCTLA4Ig. Gene transfers occurred 6 weeks before transplantation. Group D had a significantly longer liver graft survival time (> 100 days) than groups B (11.9 +/- 1.3 days) and C (11.6 +/- 1.1 days). Groups B and C showed severe rejection responses and large amounts of CD4(+) and CD8(+) T-lymphocyte infiltration, while only a mild response and few T-lymphocytes were observed in group D. There were no significant differences in interleukin-2 and interferon-gamma levels in liver grafts between groups D and C, but there were significant decreases in granzyme B and lymphotoxin beta levels in group D compared with group C. It is concluded that immunological tolerance to liver allograft could be achieved by gene transfer of rAAV-hCTLA4Ig through intramuscular injection.
Su
Z-L
ZL
Department of Hepatobiliary Surgery, Second Clinical College, Harbin Medical University, Harbin, China.
Zhong
X-Y
XY
Cui
Y-F
YF
Tai
S
S
D000818:Animals; D015703:Antigens, CD / Q000008:administration & dosage / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D060908:CTLA-4 Antigen; D000229:Dependovirus / Q000235:genetics*; D005786:Gene Expression Regulation; D006801:Humans; D007136:Immunoglobulins / Q000276:immunology*; D007273:Injections, Intramuscular; D016031:Liver Transplantation / Q000276:immunology*; D008297:Male; D009132:Muscles / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology; D015996:Survival Rate; D023001:Transplantation Tolerance / Q000276:immunology*
D015703:Antigens, CD; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D007136:Immunoglobulins; D012333:RNA, Messenger; D011994:Recombinant Proteins