Sze D M, Giesajtis G, Brown R D, Raitakari M, Gibson J, Ho J, Baxter A G, Fazekas de St Groth B, Basten A, Joshua D E
Institute of Haematology, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia.
Blood. 2001 Nov 1;98(9):2817-27. doi: 10.1182/blood.v98.9.2817.
The occurrence of clonal T cells in multiple myeloma (MM), as defined by the presence of rearrangements in the T-cell receptor (TCR)-beta chains detected on Southern blotting, is associated with an improved prognosis. Recently, with the use of specific anti-TCR-variable-beta (anti-TCRV(beta)) antibodies, the presence in MM patients of expanded populations of T cells expressing particular V(beta) regions was reported. The majority of these T-cell expansions have the phenotype of cytotoxic T cells (CD8(+)CD57(+) and perforin positive). Since V(beta) expansions can result from either a true clonal population or a polyclonal response, the clonality of CD8(+)TCRV(beta)(+) T cells was tested by TCRV(beta) complementarity-determining region 3 length analysis and DNA sequencing of the variable region of the TCR. In this report, the CD57(+) and CD57(-) subpopulations within expanded TCRV(beta)(+)CD8(+) cell populations are compared, and it is demonstrated that the CD57(+) subpopulations are generally monoclonal or biclonal, whereas the corresponding CD57(-) cells are frequently polyclonal. The oligoclonality of CD57(+) expanded CD8(+) T cells but not their CD57(-) counterparts was also observed in age-matched controls, in which the T-cell expansions were mainly CD8(-). The CD8(+)CD57(+) clonal T cells had a low rate of turnover and expressed relatively lower levels of the apoptotic marker CD95 than their CD57(-) counterparts. Taken together, these findings demonstrate that MM is associated with CD57(+)CD8(+) T-cell clones, raising the possibility that the expansion and accumulation of activated clonal CD8(+) T cells in MM may be the result of persistent stimulation by tumor-associated antigens, combined with a reduced cellular death rate secondary to reduced expression of the apoptosis-related molecule CD95.
通过Southern印迹法检测到的T细胞受体（TCR）β链重排所定义的多发性骨髓瘤（MM）中克隆性T细胞的出现与预后改善相关。最近，使用特异性抗TCR可变β（抗TCRVβ）抗体，报道了MM患者中存在表达特定Vβ区域的T细胞扩增群体。这些T细胞扩增中的大多数具有细胞毒性T细胞的表型（CD8⁺CD57⁺且穿孔素阳性）。由于Vβ扩增可能源于真正的克隆群体或多克隆反应，因此通过TCRVβ互补决定区3长度分析和TCR可变区的DNA测序来检测CD8⁺TCRVβ⁺T细胞的克隆性。在本报告中，对扩增的TCRVβ⁺CD8⁺细胞群体中的CD57⁺和CD57⁻亚群进行了比较，结果表明CD57⁺亚群通常是单克隆或双克隆的，而相应的CD57⁻细胞则经常是多克隆的。在年龄匹配的对照中也观察到CD57⁺扩增的CD8⁺T细胞的寡克隆性，而其CD57⁻对应细胞则没有，在这些对照中T细胞扩增主要是CD8⁻。与它们的CD57⁻对应细胞相比，CD8⁺CD57⁺克隆性T细胞的更新率较低，并且凋亡标志物CD95的表达水平相对较低。综上所述，这些发现表明MM与CD57⁺CD8⁺T细胞克隆相关，这增加了MM中活化克隆性CD8⁺T细胞的扩增和积累可能是肿瘤相关抗原持续刺激的结果，同时伴有凋亡相关分子CD95表达降低导致细胞死亡率降低的可能性。
