CYTOLYTIC T-LYMPHOCYTES DISPLAYING NATURAL-KILLER (NK)-LIKE ACTIVITY - EXPRESSION OF NK-RELATED FUNCTIONAL RECEPTORS FOR HLA CLASS-I MOLECULES (P58 AND CD94) AND INHIBITORY EFFECT ON THE TCR-MEDIATED TARGET-CELL LYSIS OR LYMPHOKINE PRODUCTION
CYTOLYTIC T-LYMPHOCYTES DISPLAYING NATURAL-KILLER (NK)-LIKE ACTIVITY - EXPRESSION OF NK-RELATED FUNCTIONAL RECEPTORS FOR HLA CLASS-I MOLECULES (P58 AND CD94) AND INHIBITORY EFFECT ON THE TCR-MEDIATED TARGET-CELL LYSIS OR LYMPHOKINE PRODUCTION
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DOI：
10.1093/intimm/7.4.697
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发表时间：
1995-04-01
影响因子：
4.4
通讯作者：
POGGI, A
中科院分区：
文献类型：
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作者：
MINGARI, MC;VITALE, C;POGGI, A
自然杀伤（NK）细胞表达针对限定的HLA I类等位基因组的表面受体。这些受体与靶细胞上表达的HLA I类分子之间的特异性相互作用导致NK介导的靶细胞裂解的抑制。在这份报告中，我们分析了是否有类似的机制在细胞溶解性T淋巴细胞（CTL）能够裂解NK敏感的靶细胞。筛选T细胞克隆的裂解K562靶细胞的能力。选择的克隆表达γ δ或α β TCR。这些克隆中的大多数未能裂解HLA I类+ R8/15375细胞系;然而，在加入先前描述的A6-136（IgM）或6A 4 F（ab '）（2）抗HLA I类mAb后，靶细胞被有效地裂解。在存在抗HLA I类mAb的情况下，自体植物血凝素母细胞的裂解主要发生在TCR γ δ（+）CTL。识别靶细胞上的HLA I类分子意味着在CTL克隆中表达NK相关的特异性受体。事实上，对>300个具有NK样活性的CTL克隆的表型分析显示，28%表达p58分子（对HLA-C等位基因特异性），而30%表达CD 94分子（对Bw 6特异性）。如抗p58或抗CD 94单克隆抗体（IgG同种型）对Fc γ R（+）K562靶细胞裂解的作用所揭示的，发现这些受体分子起抑制性受体的作用。此外，虽然221细胞系对CTL克隆的裂解敏感，但用Cw 3转染的221细胞不被GL 183（+）（p58）克隆裂解，从而为给定的HLA I类等位基因施加的特异性保护提供了直接证据。最后，我们表明，抗p58或抗CD 94单克隆抗体抑制T细胞活化诱导的抗TCR单克隆抗体。在TCR触发的靶细胞裂解和细胞因子肿瘤坏死因子-α产生上都检测到这种抑制活性。
Natural killer (NK) cells express surface receptors for defined groups of HLA class I alleles. The specific interaction between these receptors and HLA class I molecules expressed on target cells results in inhibition of NK-mediated target cell lysis. In this report, we analyzed whether similar mechanisms were operating in cytolytic T lymphocytes (CTLs) capable of lysing NK-sensitive target cells. T cell clones were screened for their ability to lyse K562 target cells. The selected clones expressed either gamma delta or alpha beta TCR. The majority of these clones failed to lyse the HLA class I+ R8/15375 cell line; however, upon addition of the previously described A6-136 (IgM) or 6A4 F(ab')(2) anti-HLA class I mAbs, target cells were efficiently lysed. Lysis of autologous phytohemagglutinin blasts in the presence of anti-HLA class I mAbs occurred primarily with TCR gamma delta(+) CTLs. Recognition of HLA class I molecules on target cells implies the expression of NK-related specific receptors in CTL clones. Indeed, phenotypic analysis of >300 CTL clones with NK-like activity revealed that 28% expressed p58 molecules (specific for HLA-C alleles) while 30% expressed CD94 molecules (specific for the Bw6 specificity). these receptor molecules were found to function as inhibitory receptors, as revealed by the effect of anti-p58 or anti-CD94 mAbs (of IgG isotype) on the lysis of the Fc gamma R(+) K562 target cells. In addition, while the 221 cell line was susceptible to lysis by CTL clones, 221 cells transfected with Cw3 were not lysed by GL183(+) (p58) clones, thus providing direct evidence for the specific protection exerted by given HLA class I alleles. Finally, we show that anti-p58 or anti-CD94 mAbs inhibit the T cell activation induced by anti-TCR mAbs. This inhibitory activity has been detected both on the TCR-triggered target cell lysis and on cytokine tumor necrosis factor-alpha production.