Document 0198
 DOCN  M9580198
 TI    Cellular and molecular mechanisms of human cardiac myocyte injury after
       transplantation.
 DT    9506
 AU    Ansari AA; Sundstrom JB; Kanter K; Mayne A; Villinger F; Gravanis MB;
       Herskowitz A; Dept. of Pathology and Laboratory Medicine, Winship
       Cancer; Center, Emory University, Atlanta, GA 30322, USA.
 SO    J Heart Lung Transplant. 1995 Jan-Feb;14(1 Pt 1):102-12. Unique
       Identifier : AIDSLINE MED/95244530
 AB    BACKGROUND: Fetal human cardiac myocytes or a cell line derived from
       fetal human cardiac myocytes, termed W1, even after experimental
       induction of normal levels of major histocompatibility complex class I
       and II antigens, fail to induce the activation of primary allogeneic
       responses. Therefore, our laboratory has investigated the ability of
       such MHC-expressing cardiac myocytes to induce secondary
       alloproliferative responses or to serve as target cells for cytotoxic T
       lymphocytes. METHODS: Cloned CD4+ and CD8+ T-cell lines having
       specificity for major histocompatibility complex class I and II
       molecules expressed by the fetal human cardiac myocytes and the W1 cell
       line were used in standard proliferation and cytotoxicity assays.
       RESULTS: Our data show that none of the 19 HLA-DR3 (beta 1 0301)- or
       HLA-DR15 (beta 1 1501)-specific CD4+ cloned T-cell lines reacted with
       HLA-DR3- or DR15-expressing W1 or fetal human cardiac myocytes. However,
       these CD4+ T cells did react, as expected, with similar
       HLA-DR3/DR15-expressing homozygous typing cells. Of the 16 cloned CD8+
       cytotoxic T lymphocytes with specificity for HLA-A2 and the 12 with
       specificity for HLA-A1, only two of each showed weak cytotoxicity
       against interferon gamma-pretreated HLA-A2 and A1-expressing W1 and
       fetal human cardiac myocytes, respectively. Each cloned cytotoxic T
       lymphocytes line, however, was very effective against HLA-A2 and
       A1-expressing homozygous typing cells. Although the IFN-gamma-induced W1
       and fetal human cardiac myocytes were not susceptible to cytotoxic T
       lymphocytes-mediated lysis, they were capable of inhibiting specific
       cytotoxic T lymphocytes function as defined by cold target inhibition
       studies. CONCLUSIONS: These data suggest that peptide-allo major
       histocompatibility complex presented by human cardiomyocytes is
       recognized by T cells and the these lymphocyte/myocyte interactions lead
       to immunologic ignorance.
 DE    Cell Line  CD4-Positive T-Lymphocytes/IMMUNOLOGY  CD8-Positive
       T-Lymphocytes/IMMUNOLOGY  Graft Rejection/*IMMUNOLOGY  Heart
       Transplantation/*IMMUNOLOGY  Histocompatibility Antigens Class
       I/IMMUNOLOGY  Histocompatibility Antigens Class II/IMMUNOLOGY  Human  In
       Vitro  Myocardium/CYTOLOGY/*IMMUNOLOGY  Support, Non-U.S. Gov't
       Support, U.S. Gov't, P.H.S.  T-Lymphocytes, Cytotoxic/IMMUNOLOGY
       JOURNAL ARTICLE

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