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M9550028.TXT
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1995-03-04
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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).