home *** CD-ROM | disk | FTP | other *** search
- 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).
-
-