Aa. Ansari et al., CELLULAR AND MOLECULAR MECHANISMS OF HUMAN CARDIAC MYOCYTE INJURY AFTER TRANSPLANTATION, The Journal of heart and lung transplantation, 14(1), 1995, pp. 102-112
Background: Fetal human cardiac myocytes or a cell line derived from f
etal human cardiac myocytes, termed W1, even after experimental induct
ion of ''normal'' levels of major histocompatibility complex class I a
nd II antigens, fail to induce the activation of primary allogeneic re
sponses. Therefore, our laboratory has investigated the ability of suc
h MHC-expressing cardiac myocytes to induce secondary alloproliferativ
e responses or to serve as target cells for cytotoxic T lymphocytes. M
ethods: 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 standar
d proliferation and cytotoxicity assays. Results: Our data show that n
one of the 19 HLA-DR3 (beta1 0301)- or HLA-DR15 (beta1 1501)-specific
CD4+ cloned T-cell lines reacted with HLA-DR3- or DR15-expressing W1 o
r fetal human cardiac myocytes. However, these CD4+ T cells did react,
as expected, with similar HLA-DR3/DR15-expressing homozygous typing c
ells. Of the 16 cloned CD8+ cytotoxic T lymphocytes with specificity f
or HLA-A2 and the 12 with specificity for HLA-A1, only two of each sho
wed weak cytotoxicity against interferon gamma-pretreated HLA-A2 and A
1-expressing W1 and fetal human cardiac myocytes, respectively. Each c
loned cytotoxic T lymphocytes line, however, was very effective agains
t HLA-A2 and A1-expressing homozygous typing cells. Although the IFN-g
amma-induced W1 and fetal human cardiac myocytes were not susceptible
to cytotoxic T lymphocytes-mediated lysis, they were capable of inhibi
ting specific cytotoxic T lymphocytes function as defined by cold targ
et inhibition studies. Conclusions: These data suggest that peptide-al
lo major histocompatibility complex presented by human cardiomyocytes
is recognized by T cells and the these lymphocyte/myocyte interactions
lead to immunologic ignorance.