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Titolo:
CYTOKINE MESSENGER-RNA PROFILES IN MOUSE ORTHOTOPIC LIVER-TRANSPLANTATION - GRAFT-REJECTION IS ASSOCIATED WITH AUGMENTED TH1 FUNCTION
Autore:
THAI NL; FU FM; QIAN SG; SUN H; GAO L; WANG SC; DEMETRIS AJ; WOO J; THOMSON AW; DUQUESNOY RJ; FUNG JJ;
Indirizzi:
BIOMED SCI TOWER,15TH FL,LOTHROP & TERRACE ST PITTSBURGH PA 15261 UNIV PITTSBURGH,SCH MED,PITTSBURGH TRANSPLANTAT INST PITTSBURGH PA 15213 UNIV PITTSBURGH,SCH MED,DEPT SURG PITTSBURGH PA 15213 UNIV PITTSBURGH,SCH MED,DEPT PATHOL PITTSBURGH PA 15213
Titolo Testata:
Transplantation
fascicolo: 2, volume: 59, anno: 1995,
pagine: 274 - 281
SICI:
0041-1337(1995)59:2<274:CMPIMO>2.0.ZU;2-D
Fonte:
ISI
Lingua:
ENG
Soggetto:
LYMPHOCYTE-T CLONES; INTERFERON-GAMMA; IFN-GAMMA; PERIPHERAL TOLERANCE; IMMUNE REGULATION; CELL CLONE; RESPONSES; EXPRESSION; INDUCTION; LEISHMANIASIS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
44
Recensione:
Indirizzi per estratti:
Citazione:
N.L. Thai et al., "CYTOKINE MESSENGER-RNA PROFILES IN MOUSE ORTHOTOPIC LIVER-TRANSPLANTATION - GRAFT-REJECTION IS ASSOCIATED WITH AUGMENTED TH1 FUNCTION", Transplantation, 59(2), 1995, pp. 274-281

Abstract

Although mouse liver allografts are spontaneously accepted without immunosuppression in many strain combinations, rejection can be induced by presensitization with a donor skin graft two weeks prior to transplantation. In this study, the semiquantitative reverse transcription polymerase chain reaction (RT-PCR) was used to assess the involvement ofT helper (TH) cell subsets in liver allograft acceptance by determining cytokine mRNA in the graft and spleen of recipients with (A) spontaneously accepting allografts (B) rejecting liver allografts after previous skin sensitization, and (C) syngeneic controls. Spontaneously accepted liver allografts showed upregulation of TH1 (IL-2, IFN-gamma) and TH2 (IL-4, IL-10) intragraft cytokine mRNA, which peaked at day 6 and tapered off thereafter, when compared with levels in syngeneic grafts, but both IFN-gamma and IL-10 mRNA persisted up to day 30. This cytokine mRNA profile correlated with the transient intragraft inflammation associated with spontaneously resolving rejection. Presensitized recipients that rejected their grafts revealed marked upregulation of TH1(IL-2 and IFN-gamma) and TH2 (IL-4, IL-6) intragraft cytokine mRNAs compared with spontaneously accepting recipients, although IL-10 mRNA levels showed no differences between the two groups, The most striking difference was seen in IFN-gamma levels, which correlated well with the preferential deposition of IgG2a antibody isotype in the rejecting compared with the spontaneously accepting liver allograft recipients, These results suggested an association between liver allograft rejection and enhanced TH1 cytokine immune response. The ability to reject liver allografts by the adoptive transfer of splenocytes, but not serum, from a sensitized mouse ruled out preformed antibodies alone as a cause of rejection, However, spleen cytokine mRNA profiles showed no differences or trends in TH1 or TH2 expression in spontaneously accepting versus rejecting recipients, which suggested that the spleen is not a major site of alloreactive immune expansion. These data suggest that spontaneous acceptance of mouse liver allografts is associated with an insufficient intragraft TH1 cytokine response, the cause of which is currently under investigation.

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Documento generato il 19/09/20 alle ore 15:06:08