Bianchi A, Montacchini L, Barral P, Borrione P, Attisano C, Orsini E, Boccadoro M, Pileri A, Massaia M
Dipartimento di Medicina ed Oncologia Sperimentale, Università di Torino, Ospedale Molinette, Italy.
Br J Haematol. 1995 Jul;90(3):625-32. doi: 10.1111/j.1365-2141.1995.tb05594.x.
A large expansion of activated T cells (CD3+CD25+) with the potential to act as anti-tumour effector cells is inducible in multiple myeloma (MM) patients by culturing bone marrow mononuclear cells (BMMCs) with the anti-CD3 monoclonal antibody (mAb) OKT3. The aim of this study was to provide a greater characterization of CD3-activated T cells. On day 6, most T cells coexpressed the CD11a, CD18, CD54, CD45R0 antigens and consisted of activated (CD25+) CD4+ and CD8+ cells in nearly equal proportions. Kinetics studies showed that CD4+CD25+ cells proliferated more rapidly and peaked earlier than CD8+CD25+ cells. When experiments were performed with purified subpopulations by removing CD4+ cells (resulting in CD8+ BMMCs) or by removing CD8+ cells (resulting in CD4+ BMMCs). T-cell activation and autologous plasma cell decrease were observed in CD4+ BMMCs only. Transwell cultures showed that CD4 help was necessary to make CD8+ BMMCs susceptible to CD3 stimulation. Relevant amounts of IL-2 were found in the supernatants of CD4+ BMMCs cultures, whereas no secretion of IL-4 was detected, indicating a Th1-like profile of CD3-activated CD4+ cells. These data indicate that CD4+ cells proliferate earlier and provide optimal help to induce the subsequent expansion of CD8+ cells after CD3 stimulation of MM BMMCs. Adequate stimulation of CD4+ cells is therefore essential in any strategy aiming to recover T-cell-mediated immunity in MM.
通过用抗CD3单克隆抗体（mAb）OKT3培养骨髓瘤（MM）患者的骨髓单个核细胞（BMMCs），可诱导出大量具有抗肿瘤效应细胞潜能的活化T细胞（CD3 + CD25 +）。本研究的目的是更全面地表征CD3活化的T细胞。在第6天，大多数T细胞共表达CD11a、CD18、CD54、CD45R0抗原，并且由活化的（CD25 +）CD4 +和CD8 +细胞组成，比例几乎相等。动力学研究表明，CD4 + CD25 +细胞增殖更快，且比CD8 + CD25 +细胞更早达到峰值。当通过去除CD4 +细胞（得到CD8 + BMMCs）或去除CD8 +细胞（得到CD4 + BMMCs）对纯化的亚群进行实验时，仅在CD4 + BMMCs中观察到T细胞活化和自体浆细胞减少。Transwell培养表明，CD4辅助对于使CD8 + BMMCs对CD3刺激敏感是必要的。在CD4 + BMMCs培养上清液中发现了适量的IL-2，而未检测到IL-4的分泌，表明CD3活化的CD4 +细胞具有类似Th1的特征。这些数据表明，CD4 +细胞增殖更早，并在MM BMMCs受到CD3刺激后为诱导CD8 +细胞的后续扩增提供最佳辅助。因此，在任何旨在恢复MM中T细胞介导免疫的策略中，充分刺激CD4 +细胞至关重要。
