CLONAL ANALYSIS OF HUMAN CYTO-TOXIC LYMPHOCYTES-T - T4+ AND T8+ EFFECTOR T-CELLS RECOGNIZE PRODUCTS OF DIFFERENT MAJOR HISTOCOMPATIBILITY COMPLEX REGIONS

CLONAL ANALYSIS OF HUMAN CYTO-TOXIC LYMPHOCYTES-T - T4+ AND T8+ EFFECTOR T-CELLS RECOGNIZE PRODUCTS OF DIFFERENT MAJOR HISTOCOMPATIBILITY COMPLEX REGIONS
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DOI:
10.1073/pnas.79.14.4395
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发表时间:
1982-01-01
期刊:
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子:
--
通讯作者:
REINHERZ, EL
REINHERZ, EL
中科院分区:
其他
文献类型:
--
作者:
MEUER, SC;SCHLOSSMAN, SF;REINHERZ, EL

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同种反应性人T淋巴细胞在软琼脂中或通过有限稀释进行克隆,随后用白细胞介素2和gtoreq的同种抗原进行增殖。 8个月。通过间接免疫荧光,每个克隆都与抗 Ia 抗体以及抗 T3 和抗 T11 的 T 细胞特异性抗体发生反应,并表达 T4 或 T8 抗原。所有 15 个 T8+ 克隆对致敏同种异体抗原均具有高度细胞毒性。 7 个 T4+ 克隆中只有 2 个介导细胞毒性效应子功能。 T8+克隆和亚克隆的特异性在一组分型细胞上进行分析,并通过刺激同种抗原上主要组织相容性复合体(MHC)决定簇的抗体封闭研究进行分析。 T8+克隆杀死与原始刺激细胞共享I类MHC抗原(HLA-A、B)的靶标,细胞毒性T4+克隆针对II类MHC抗原(Ia相关)。同种异体靶细胞与针对非多态性HLAα-链决定簇的单克隆抗体的预温育抑制了T8+克隆的杀伤作用,但不影响T4+细胞毒性功能。以相反的方式,针对同一靶细胞上共同框架结构的抗 Ia 抗体可阻断 T4+ 克隆的杀伤作用,但不能阻断 T8+ 克隆的杀伤作用。 T4+ 和 T8+ T 淋巴细胞显然具有不同类别 MHC 抗原的受体,细胞毒性 T4+ 亚群可能在人类移植和自身免疫性疾病中发挥重要作用。
Alloreactive human T lymphocytes were cloned in soft agar or by limiting dilution and subsequently propagated with interleukin 2 and alloantigen for .gtoreq. 8 mo. By indirect immunofluorescence every clone was reactive with anti-Ia antibodies and the T cell-specific antibodies anti-T3 and anti-T11 and expressed either T4 or T8 antigens. All 15 T8+ clones were highly cytotoxic for the sensitizing alloantigen. Only 2 of 7 T4+ clones mediated cytotoxic effector function. The specificity of T8+ clones and subclones was analyzed on a panel of typing cells and by antibody blocking studies of major histocompatibility complex (MHC) determinants on the stimulating alloantigen. T8+ clones killed targets that shared class I MHC antigens (HLA-A,B) with the original stimulator cells, cytotoxic T4+ clones were directed at class II MHC antigens (Ia-related). Preincubation of the allogeneic target cell with a monoclonal antibody to a nonpolymorphic HLA .alpha.-chain determinant inhibited killing by the T8+ clones but did not affect T4+ cytotoxic function. In a reciprocal fashion, anti-Ia antibodies to common framework structures on the same target cell blocked killing by T4+ but not by T8+ clones. T4+ and T8+ T lymphocytes apparently have receptors for different classes of MHC antigens and cytotoxic T4+ subpopulations might be important in human transplantation and autoimmune disorders.