Document 0028
 DOCN  M9550028
 TI    Cytokine mRNA profiles in mouse orthotopic liver transplantation. Graft
       rejection is associated with augmented TH1 function.
 DT    9505
 AU    Thai NL; Fu F; Qian S; Sun H; Gao L; Wang SC; Demetris AJ; Woo J;
       Thomson AW; Duquesnoy RJ; et al; Pittsburgh Transplantation Institute,
       University of Pittsburgh; School of Medicine, Pennsylvania 15213.
 SO    Transplantation. 1995 Jan 27;59(2):274-81. Unique Identifier : AIDSLINE
       MED/95141395
 AB    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 (RTPCR) was used to assess the
       involvement of T 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.
 DE    Animal  Comparative Study  Cytokines/*GENETICS/IMMUNOLOGY/METABOLISM
       Graft Rejection/*IMMUNOLOGY/PHYSIOPATHOLOGY  Immunotherapy, Adoptive
       Liver/METABOLISM  Liver Transplantation/*IMMUNOLOGY  Male  Mice  Mice,
       Inbred C3H  Mice, Inbred C57BL  Phosphorus Radioisotopes  Polymerase
       Chain Reaction  Reverse Transcriptase  RNA, Messenger/*METABOLISM  Skin
       Transplantation/IMMUNOLOGY  Spleen/CYTOLOGY/METABOLISM  Th1
       Cells/IMMUNOLOGY/METABOLISM/*PHYSIOLOGY  Up-Regulation
       (Physiology)/PHYSIOLOGY  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).