Comparison of anti-CD3 and anti-CD28-coated beads with soluble anti-CD3 for expanding human T cells: differing impact on CD8 T cell phenotype and responsiveness to restimulation.
Comparison of anti-CD3 and anti-CD28-coated beads with soluble anti-CD3 for expanding human T cells: differing impact on CD8 T cell phenotype and responsiveness to restimulation.
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DOI：
10.1186/1479-5876-8-104
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发表时间：
2010-10-26
影响因子：
7.4
通讯作者：
Kurlander RJ
中科院分区：
文献类型：
--
作者：
Li Y;Kurlander RJ
扩增病毒或肿瘤特异性T细胞而不损害其功能能力的能力对于机会性感染或肿瘤患者的成功过继转移免疫治疗至关重要。仔细比较可以帮助确定更适合特定临床环境的扩张方法，并确定需要新创新的复发性缺陷。我们比较了包被有抗-CD 3和抗-CD 28的磁珠（抗-CD 3/CD 28珠）和可溶性抗-CD 3加混合单核细胞（称为快速扩增方案或REP）在扩增正常人T细胞中的功效。抗CD 3/CD 28珠和可溶性抗CD 3均促进广泛扩增。珠粒刺激更大的CD 4细胞生长（在第21天的几何平均值为56倍对27倍（p < 0.01）），但两者都刺激类似的CD 8扩增（189倍对186倍）。表型上，珠处理的CD 4和CD 8 T细胞和抗CD 3处理的CD 4细胞通常在第14天呈现效应子/效应子记忆表型。相比之下，抗CD 3处理的CD 8细胞亚群（来自幼稚细胞）保留了比匹配的珠处理细胞更高的CD 45 RA、CD 27和CCR 7表达，尽管扩增相当。这些细胞通过CD 27的存在、CD 57的不存在以及它们在刺激后不能产生细胞因子而与CD 45 RA+终末分化效应细胞明显区分。当用于扩增先前刺激的细胞时，抗CD 3加自体MNC产生的抗原诱导的CD 8细胞细胞死亡少得多，而CD 8扩增显著多于珠。抗-CD 3/CD 28珠对于扩增CD 4细胞是高度有效的，但是可溶性抗-CD 3对于扩增CD 8 T细胞具有显著的潜在优势，特别是在需要保留表型“年轻”的CD 8细胞的情况下，或者在感兴趣的T细胞在最近的过去已经在体外或体内被抗原刺激的情况下。
The ability to expand virus- or tumor-specific T cells without damaging their functional capabilities is critical for success adoptive transfer immunotherapy of patients with opportunistic infection or tumor. Careful comparisons can help identify expansion methods better suited for particular clinical settings and identify recurrent deficiencies requiring new innovation. We compared the efficacy of magnetic beads coated with anti-CD3 and anti-CD28 (anti-CD3/CD28 beads), and soluble anti-CD3 plus mixed mononuclear cells (designated a rapid expansion protocol or REP) in expanding normal human T cells. Both anti-CD3/CD28 beads and soluble anti-CD3 promoted extensive expansion. Beads stimulated greater CD4 cell growth (geometric mean of 56- versus 27-fold (p < 0.01) at day 21) but both stimulated similar CD8 expansion (189- versus 186-fold). Phenotypically, bead-treated CD4 and CD8 T cells and anti-CD3-treated CD4 cells typically assumed an effector/effector memory phenotype by day 14. By comparison, a subset of anti-CD3-treated CD8 cells, derived from naïve cells, retained much greater expression of CD45RA, CD27 and CCR7, than matched bead-treated cells despite comparable expansion. These cells were clearly distinguishable from CD45RA+ terminally differentiated effector cells by the presence of CD27, the absence of CD57 and their inability to produce cytokines after stimulation. When used to expand previously stimulated cells, anti-CD3 plus autologous MNCs produced much less antigen-induced cell death of CD8 cells and significantly more CD8 expansion than beads. Anti-CD3/CD28 beads are highly effective for expanding CD4 cells, but soluble anti-CD3 has significant potential advantages for expanding CD8 T cells, particularly where preservation of phenotypically "young" CD8 cells would be desirable, or where the T cells of interest have been antigen-stimulated in vitro or in vivo in the recent past.
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影响因子：
4.4
作者：
Hamann, D;Kostense, S;van Lier, RAW
通讯作者：
van Lier, RAW
DOI：
10.1084/jem.20040717
发表时间：
2004-12-06
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Ochsenbein AF;Riddell SR;Brown M;Corey L;Baerlocher GM;Lansdorp PM;Greenberg PD
通讯作者：
Greenberg PD
影响因子：
3.9
作者：
Dudley, ME;Wunderlich, JR;Rosenberg, SA
通讯作者：
Rosenberg, SA
影响因子：
20.3
作者：
Carrasco, Javier;Godelaine, Daniele;van der Bruggen, Pierre
通讯作者：
van der Bruggen, Pierre
影响因子：
6.4
作者：
Fleischer, J;Soeth, E;Ernst, M
通讯作者：
Ernst, M