Kay N, Leong T, Kyle R A, Greipp P, Van Ness B, Bone N, Oken M M
Virginia Piper Cancer Institute, Minneapolis, MN, USA.
Leuk Lymphoma. 1999 Mar;33(1-2):127-33. doi: 10.3109/10428199909093733.
Previous investigations have demonstrated that an expanding circulating T cell population is able to modulate the malignant clone in multiple myeloma. More recently, an expansion of T cell subsets exhibiting a restricted T cell repertoire has been detected in some MM patients. To further elucidate if a selected T cell expansion occurs in MM, we studied the T cell receptor (TCR) variable (V) region expression from a cohort of previously diagnosed and treated MM patients (N=37). The latter was done by assessing the reactivity of a panel of monoclonal antibodies specific for different V region families (alpha or beta) in combination with anti-CD4 or anti-CD8, for purified blood T cells from MM patients. TCR V region usage in MM patients was compared to blood T cells from age matched (N=13) control individuals. The multivariate analysis of variance did not uncover a difference for distribution of TCR V region usage between the normal controls and the MM cohort. However, there were individual MM patients who had expanded T cells with specific TCR V region expression when compared to the control group. Several MM patients had multiple, expanded CD4 and/or CD8 subsets based on TCR V region expression. The majority of MM patients had expanded T cell subsets that constituted less than 10% of the total blood T cell pool. However, a few MM patients (N=3) had larger percentages (range 34-84%) of these expanded T cell subsets within their blood T (CD3+) cells. The stage of disease and treatment status (currently on or off therapy) did not associate with the pattern of restricted T cell repertoire. Finally, a smaller cohort of newly diagnosed, untreated MM patients (N=13) also demonstrated an expanded T cell repertoire. However, these patients had more CD4 than CD8 cell subsets involved in the altered V region expression in several Vbeta families. Thus, these results add to the evidence that this malignant B cell disorder whether newly diagnosed or of longer duration, may be accompanied by an altered T cell repertoire characterized in part by expanded T cell clones.
先前的研究表明，不断扩大的循环T细胞群体能够调节多发性骨髓瘤中的恶性克隆。最近，在一些MM患者中检测到表现出受限T细胞库的T细胞亚群扩增。为了进一步阐明MM中是否发生了特定T细胞扩增，我们研究了一组先前诊断和治疗过的MM患者（N = 37）的T细胞受体（TCR）可变（V）区表达。通过评估一组针对不同V区家族（α或β）的单克隆抗体与抗CD4或抗CD8结合对MM患者纯化血液T细胞的反应性来完成后者。将MM患者的TCR V区使用情况与年龄匹配的（N = 13）对照个体的血液T细胞进行比较。多变量方差分析未发现正常对照组和MM队列之间TCR V区使用分布的差异。然而，与对照组相比，有个别MM患者具有特定TCR V区表达的扩增T细胞。基于TCR V区表达，几名MM患者有多个扩增的CD4和/或CD8亚群。大多数MM患者的扩增T细胞亚群占总血液T细胞池的比例不到10%。然而，少数MM患者（N = 3）血液T（CD3 +）细胞中这些扩增T细胞亚群的百分比更高（范围为34 - 84%）。疾病阶段和治疗状态（目前正在接受治疗或未接受治疗）与受限T细胞库模式无关。最后，一小群新诊断、未治疗的MM患者（N = 13）也表现出扩增的T细胞库。然而，在几个Vβ家族中，这些患者参与V区表达改变的CD4细胞亚群比CD8细胞亚群更多。因此，这些结果进一步证明，这种恶性B细胞疾病无论是新诊断的还是病程较长的，都可能伴有改变的T细胞库，其部分特征是T细胞克隆扩增。
