Tumor Antigen-specific T-cells are Present in the CD8αα+ T-cell Effector-memory Pool
Tumor Antigen-specific T-cells are Present in the CD8αα+ T-cell Effector-memory Pool
复制标题
DOI：
10.1097/cji.0b013e31818883a1
复制
发表时间：
2008-11-01
影响因子：
3.9
通讯作者：
Maeurer, Markus J.
中科院分区：
文献类型：
--
作者：
Magalhaes, Isabelle;Vudattu, Nalini Kumar;Maeurer, Markus J.
最近已经证明，小鼠中的CD 8（+）T细胞记忆形成与T细胞的CD 8 α α同源二聚体表达相关。到目前为止，关于CD 8 α α（+）T细胞在人类中的临床意义的知识是有限的。我们在接受基于肽的疫苗接种的黑色素瘤患者的纵向采集的血液样本中评估了CD 8 α α（+）T细胞在肿瘤特异性细胞免疫应答中的作用。表型分析显示，T细胞表达的CD 8 α α（+）随时间推移而稳定，并与CD 45 RA（+/-）CCR 7（-）效应记忆特征相关。通过四聚体技术在CD 8 α α（+）T细胞区室中鉴定Melan-A/ MART-1特异性T细胞。细胞内细胞因子产生的检测（白细胞介素-2，干扰素-γ，和肿瘤坏死因子-α）在佛波醇12-肉豆蔻酸酯13-乙酸盐-离子霉素刺激后的CD 8 α α（+）和CD 8 α β（+）T细胞中的表达，揭示了CD 8 α α（+）T细胞显示出独特的细胞因子产生模式，（肿瘤坏死因子-α和干扰素-γ的产生）与CD 8 α β（+）T细胞相比。T细胞受体-CDR 3长度分析显示，与Melan-A/MART-1特异性CD 8 α β（+）T细胞相比，Melan-A/MART-1特异性CD 8 α α（+）T细胞显示出相似的T细胞受体库。我们的研究结果表明，CD 8 α α（+）T细胞代表了黑色素瘤患者外周循环中CD 45 RA（+/-）效应记忆细胞的一个区室，并表明CD 8 α α（+）T细胞可能来源于下调CD 8 β链表达的CD 8（+）T细胞。CD 8 α α（+）和四聚体特异性T细胞可以代表测量长期抗原特异性T细胞记忆的有价值的标志物。
CD8(+) T-cell memory formation has recently been demonstrated to be associated with CD8 alpha alpha homodimer expression by T-cells in mice. Up to now, the knowledge about the clinical significance of CD8 alpha alpha(+) T-cells in humans is limited. We assessed in longitudinally collected blood samples from patients with melanoma, who underwent a peptide-based vaccination, the role of CD8 alpha alpha(+) T-cells in tumor-specific cellular immune responses. Phenotypic analysis showed that the expression of CD8 alpha alpha(+) by T-cells was stable over time and associated with a CD45RA(+/-)CCR7(-) effector-memory profile. Melan-A/ MART-1-specific T-cells were identified in the CD8 alpha alpha(+) T-cell compartment by tetramer technology. Detection of intracellular cytokine production (interleukin-2, interferon-gamma, and tumor necrosis factor-alpha) upon phorbol 12-myristate 13-acetate-iono-mycin stimulation in CD8 alpha alpha(+) and CD8 alpha beta(+) T-cells revealed that CD8 alpha alpha(+) T-cells show a unique cytokine production pattern (tumor necrosis factor-alpha and interferon-gamma production) as compared with CD8 alpha beta(+) T-cells. T-cell receptor-CDR3 length analysis revealed that Melan-A/MART-1-specific CD8 alpha alpha(+) T-cells showed a similar T-cell receptor-repertoire as compared with Melan-A/MART-1-specific CD8 alpha beta(+) T-cells. Our results show that CD8 alpha alpha(+) T-cells represent a compartment of CD45RA(+/-) effector-memory cells in the peripheral circulation of patients with melanoma and suggest that CD8 alpha alpha(+) T-cells may originate from CD8(+) T-cells that have down-regulated the expression of the CD8P chain. CD8 alpha alpha(+) and tetramer-specific T-cells may represent a valuable marker to gauge long-term antigen- specific T-cell memory.