Cellular and molecular mechanisms of human cardiac myocyte injury after transplantation.
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.
Ansari
A A
AA
Dept. of Pathology and Laboratory Medicine, Winship Cancer Center, Emory University, Atlanta, GA 30322, USA.
Sundstrom
J B
JB
Kanter
K
K
Mayne
A
A
Villinger
F
F
Gravanis
M B
MB
Herskowitz
A
A
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D006084:Graft Rejection / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D066298:In Vitro Techniques; D009206:Myocardium / Q000166:cytology / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II