       Document 0860
 DOCN  M9620860
 TI    Donor specific bone marrow cells suppress lymphocyte reactivity to donor
       antigens and differentially modulate TH1 and TH2 cytokine gene
       expression in the responder cell population.
 DT    9602
 AU    Lagoo-Deenadayalan S; Lagoo AS; Lemons JA; Lorenz HM; Bass JD; McDaniel
       DO; Hardy KJ; Barber WH; Department of Surgery, University of
       Mississippi Medical Center,; Jackson 39216, USA.
 SO    Transpl Immunol. 1995 Jun;3(2):124-34. Unique Identifier : AIDSLINE
       MED/96103421
 AB    Previous studies have shown that post-transplantation infusion of donor
       specific bone marrow following a non-specific potent immunosuppressive
       agent such as antilymphocyte globulin (ALG) can significantly enhance
       graft survival compared to ALG alone. This enhancement remains variable
       and is thought to occur through the induction of specific partial
       tolerance to the renal allograft, but the underlying cellular mechanisms
       have not been clearly identified. In order to improve the efficacy of
       this specific immunosuppressive treatment and to study the events
       leading to enhanced allograft survival, we sought to establish a simple
       in vitro model based on a mixed lymphocyte reaction (MLR). We show that
       cellular proliferation seen in a normal MLR can be suppressed by
       addition of donor specific bone marrow cells (BMC). Significantly, this
       suppression is not observed with either third party BMC or donor
       specific peripheral blood mononuclear cells (PBMC). We have defined the
       optimum conditions of bone marrow infusion regarding number of BMC,
       their handling and culture, and simple enrichment procedures. Using a
       semiquantitative polymerase chain reaction assay, we have studied the
       cytokine gene expression in MLR modulated by donor specific BMC. In an
       unmodified allogeneic response, the responder cells show increased
       expression of interleukin-2 (IL-2) gamma-interferon IFN-gamma and
       receptor (IL-2R) mRNA, and no IL-10 mRNA. When responder cells are
       cultured with BMC of the stimulator, there is a 256-fold decrease in
       IL-2 mRNA, and a 64-fold decrease in IFN-gamma and IL-2R mRNA. There is
       also a 64-fold increase in IL-10 mRNA. This effect is even more marked
       when the BMC are depleted of CD3+ cells. The kinetics of addition of
       donor specific BMC to the normal allogeneic MLR culture and specificity
       of the action of BMC are also elucidated. Our data suggest that the
       enhancement of graft survival observed with donor BMC may operate
       through decreased proliferation of reactive T cell clones (due to
       decreased IL-2/IL-2R) and suppressed monocyte functions (due to
       decreased IFN-gamma and increased IL-10 gene expression).
 DE    Antigens, CD3/ANALYSIS  Bone Marrow/CYTOLOGY/IMMUNOLOGY  Bone Marrow
       Transplantation/*IMMUNOLOGY/PATHOLOGY  Cell Division/DRUG EFFECTS
       Cells, Cultured  Cryopreservation  Cytokines/*GENETICS/METABOLISM
       Fibroblast Growth Factor, Acidic/PHARMACOLOGY  Granulocyte-Macrophage
       Colony-Stimulating Factor/PHARMACOLOGY  Haplotypes  Human  HLA
       Antigens/GENETICS/*IMMUNOLOGY  *Immune Tolerance/GENETICS  Kinetics
       *Lymphocyte Culture Test, Mixed  Lymphocyte Depletion  Phenotype
       Support, Non-U.S. Gov't  Support, U.S. Gov't, P.H.S.  Th1
       Cells/IMMUNOLOGY/*METABOLISM  Th2 Cells/IMMUNOLOGY/*METABOLISM  Tissue
       Donors  JOURNAL ARTICLE

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

