Mollet L, Fautrel B, Leblond V, Bergeron F, Merle-Béral H, Baumelou E, Hubert P, Debré P, Autran B
Laboratoire d'Immunologie Cellulaire et Tissulaire, CNRS-UMR 7627, Hôpital Pitié-Salpétriêre, Paris, France.
Leukemia. 1999 Feb;13(2):230-40. doi: 10.1038/sj.leu.2401266.
Leukemic T-LGL (large granular lymphocyte) composed of clonal CD3+ TCR alphabeta+ CD8+ CD57+ cells were compared with oligoclonally CD3+ CD8hi+ CD57- lymphocytes expanded after BMT. Leukemic CD3+ CD8hi+ CD57+ LGL showed several phenotypic differences such as an upregulation of CD16 and adhesion molecules (mainly CD11c, CD58 and CD54), activation markers and an exclusive CD45RA isoform expression. Unstimulated CD3+ CD8+ CD57+ LGL from both leukemic and BMT donors spontaneously developed an ex vivo CTL-like CD3-redirected cytotoxicity but no NK cell activity. Different stimuli (PHA, PMA or rhIL-2) induced similar cytotoxic profiles after a 6-day culture involving a CD3-redirected lysis predominating over a low NK cell activity. However, culture of leukemic LGL with these stimuli allowed either a 2 week persistence (PMA or rhIL-2) of CD8+ CD57+ LGL or their disappearance after 3 days (PHA). Furthermore, leukemic CD8hi+ CD57+ T lymphocytes produced an inhibitor of cytotoxic functions as previously described for BMT recipients' CD8+ CD57+ cells. Thus, despite some phenotypic differences between both cell sources, leukemic CD57+ T-LGL display the same functional characteristics of cytotoxic effector and immunoregulatory T cells as CD8+ CD57+ T cells from BMT recipients which might represent their normal counterpart.
将由克隆性CD3⁺ TCRαβ⁺ CD8⁺ CD57⁺细胞组成的白血病性T大颗粒淋巴细胞(LGL)与骨髓移植(BMT)后寡克隆性扩增的CD3⁺ CD8hi⁺ CD57⁻淋巴细胞进行比较。白血病性CD3⁺ CD8hi⁺ CD57⁺ LGL表现出一些表型差异,如CD16和黏附分子(主要是CD11c、CD58和CD54)上调、激活标志物以及独特的CD45RA异构体表达。来自白血病患者和BMT供者的未刺激的CD3⁺ CD8⁺ CD57⁺ LGL在体外自发产生类似CTL的CD3重定向细胞毒性,但无NK细胞活性。不同刺激(PHA、PMA或rhIL-2)在6天培养后诱导出相似的细胞毒性谱,其中CD3重定向裂解占主导,NK细胞活性较低。然而,用这些刺激物培养白血病性LGL,要么使CD8⁺ CD57⁺ LGL持续2周(PMA或rhIL-2),要么在3天后消失(PHA)。此外,白血病性CD8hi⁺ CD57⁺ T淋巴细胞产生一种细胞毒性功能抑制剂,正如先前对BMT受者的CD8⁺ CD57⁺细胞所描述的那样。因此,尽管两种细胞来源存在一些表型差异,但白血病性CD57⁺ T-LGL与BMT受者的CD8⁺ CD57⁺ T细胞一样,具有细胞毒性效应细胞和免疫调节性T细胞的相同功能特征,而后者可能代表其正常对应物。