Ansari A A, Sundstrom J B, Kanter K, Mayne A, Villinger F, Gravanis M B, Herskowitz A
Dept. of Pathology and Laboratory Medicine, Winship Cancer Center, Emory University, Atlanta, GA 30322, USA.
J Heart Lung Transplant. 1995 Jan-Feb;14(1 Pt 1):102-12.
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.
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.
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.
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.
人胎儿心肌细胞或源自人胎儿心肌细胞的细胞系（称为W1），即使在实验诱导主要组织相容性复合体I类和II类抗原达到“正常”水平后，也无法诱导原发性同种异体反应的激活。因此，我们实验室研究了这种表达MHC的心肌细胞诱导继发性同种异体增殖反应或作为细胞毒性T淋巴细胞靶细胞的能力。
对人胎儿心肌细胞和W1细胞系表达的主要组织相容性复合体I类和II类分子具有特异性的克隆CD4+和CD8+ T细胞系用于标准增殖和细胞毒性测定。
我们的数据表明，19个HLA-DR3（β1 0301）或HLA-DR15（β1 1501）特异性CD4+克隆T细胞系中没有一个与表达HLA-DR3或DR15的W1或人胎儿心肌细胞发生反应。然而，正如预期的那样，这些CD4+ T细胞确实与表达类似HLA-DR3/DR15的纯合分型细胞发生了反应。在16个对HLA-A2具有特异性的克隆CD8+细胞毒性T淋巴细胞和12个对HLA-A1具有特异性的细胞中，每种分别只有两个对干扰素γ预处理的表达HLA-A2和A1的W1和人胎儿心肌细胞表现出微弱的细胞毒性。然而，每个克隆的细胞毒性T淋巴细胞系对表达HLA-A2和A1的纯合分型细胞都非常有效。虽然干扰素γ诱导的W1和人胎儿心肌细胞不易受到细胞毒性T淋巴细胞介导的裂解，但它们能够抑制冷靶抑制研究定义的特异性细胞毒性T淋巴细胞功能。
这些数据表明，人心肌细胞呈递的肽-同种异体主要组织相容性复合体被T细胞识别，并且这些淋巴细胞/心肌细胞相互作用导致免疫忽视。
