通过CD3/TCR复合物的多价交联检测多发性骨髓瘤中的高反应性T细胞。

Detection of hyperreactive T cells in multiple myeloma by multivalent cross-linking of the CD3/TCR complex.

作者信息

Massaia M, Bianchi A, Attisano C, Peola S, Redoglia V, Dianzani U, Pileri A

机构信息

Dipartimento di Medicina e Oncologia Sperimentale, Ospedale Molinette, Torino, Italy.

出版信息

Blood. 1991 Oct 1;78(7):1770-80.

PMID:1832993

Abstract

Cellular immunity was investigated in 43 patients with multiple myeloma (MM) by assessing 3HTdR uptake induced by monocyte-dependent [CD3 monoclonal antibodies (MoAbs), phytohemagglutinin (PHA)] and monocyte-independent (CD2 MoAbs, ionomycin + phorbolester) stimulations. The former were evaluated in peripheral blood mononuclear cells (PBMNC) and purified T cells; the latter were evaluated in purified T-cell preparations only. MM showed significantly lower PBMNC responses to PHA (P less than .001), soluble OKT3 (CD3) (P = .01), and immobilized OKT3 MoAbs (P = .01). On purification of T cells, MM responses were still defective to soluble T11(2) + T11(3) (CD2) MoAbs (P = .004), phorbol myristate acetate (PMA) plus ionomycin (P less than .001), but significantly higher to plastic-immobilized OKT3 (P = .004). In some MM, 3HTdR uptake, interleukin-2 (IL-2) receptor (CD25) expression, and IL-2 production were as high on stimulation with plastic-immobilized OKT3 as that observed in normal subjects under optimal conditions (ie, plastic-immobilized OKT3 plus accessory signals). CD3 hyperreactivity correlated with the number of CD8+ HLA-DR+ cells in MM T-cell preparations. MM patients with more than 10% CD8+ HLA-DR+ cells had significantly higher responses to immobilized OKT3 (P less than .001), but lower responses to T11(2) plus T11(3) (P = .01), and PMA plus ionomycin (P = .03) than patients with less than 10% CD8+ HLA-DR+ cells. Phenotyping of CD45RA (naive) and CD45R0 (memory) expressions in resting MM T cells showed a lower ratio of CD45RA to CD45R0 in both CD4 (P less than .05) and CD8 (P less than .001) subpopulations. These data indicate that (a) some MM T cells require significantly fewer accessory signals (if any) to express the IL-2 receptor fully, secrete IL-2, and proliferate on multivalent cross-linking of the CD3/TCR complex; and (b) this peculiar state of activation is associated with high HLA-DR expression in CD8+ lymphocytes.

摘要

通过评估单核细胞依赖性刺激（抗CD3单克隆抗体（MoAbs）、植物血凝素（PHA））和单核细胞非依赖性刺激（抗CD2 MoAbs、离子霉素+佛波酯）诱导的3HTdR摄取，对43例多发性骨髓瘤（MM）患者的细胞免疫进行了研究。前者在外周血单个核细胞（PBMNC）和纯化的T细胞中进行评估；后者仅在纯化的T细胞制剂中进行评估。MM患者的PBMNC对PHA（P<0.001）、可溶性OKT3（CD3）（P=0.01）和固定化OKT3 MoAbs（P=0.01）的反应显著降低。在T细胞纯化后，MM患者对可溶性T11(2)+T11(3)（CD2）MoAbs（P=0.004）、佛波醇肉豆蔻酸酯乙酸酯（PMA）加离子霉素（P<0.001）的反应仍然存在缺陷，但对塑料固定化OKT3的反应显著更高（P=0.004）。在一些MM患者中，塑料固定化OKT3刺激下的3HTdR摄取、白细胞介素-2（IL-2）受体（CD25）表达和IL-2产生与正常受试者在最佳条件下（即塑料固定化OKT3加辅助信号）观察到的一样高。CD3高反应性与MM T细胞制剂中CD8+HLA-DR+细胞的数量相关。CD8+HLA-DR+细胞超过10%的MM患者对固定化OKT3的反应显著更高（P<0.001），但对T11(2)加T11(3)（P=0.01）和PMA加离子霉素（P=0.03）的反应低于CD8+HLA-DR+细胞少于10%的患者。静息MM T细胞中CD45RA（初始）和CD45R0（记忆）表达的表型分析显示，CD4（P<0.05）和CD8（P<0.001）亚群中CD45RA与CD45R0的比例均较低。这些数据表明：（a）一些MM T细胞在CD3/TCR复合物多价交联时，表达IL-2受体、分泌IL-2和增殖所需的辅助信号显著减少（如果有的话）；（b）这种特殊的激活状态与CD8+淋巴细胞中高HLA-DR表达相关。