Imai Naoko, Ikeda Hiroaki, Tawara Isao, Shiku Hiroshi
Department of Immuno-Gene Therapy, Mie University Graduate School of Medicine, Tsu, Japan.
Eur J Immunol. 2009 Jan;39(1):241-53. doi: 10.1002/eji.200838824.
It is becoming increasingly evident that the multifunctionality of effector cells at the single-cell level is an important factor to predict the quality of T-cell response in immunological protection. The significance of the multifunctionality of T cells in anti-tumor immunity, however, remains unclear. Here, we assessed the IFN-gamma and TNF-alpha production and CD107a mobilization in adoptively transferred tumor-antigen-specific CD8(+) T cells at the single-cell level. Tumor growth of the murine fibrosarcoma CMS5 was found to limit the induction of multifunctionality in the transferred cells. These cells exhibited insufficient acquisition of the CD25(high)GITR(high)CD62L(low) phenotype and reduced infiltration in tumor. Depletion of Treg facilitated the induction of high multifunctionality of the transferred cells even in the hosts with progressing tumor, leading to enhanced tumor regression. The multifunctionality of the transferred cells correlated with in vivo CTL activity, and T cells with high multifunctionality harvested from hosts with successful therapy induced tumor regression when re-transferred into the tumor-bearing hosts. These data suggest that the appearance of multifunctional CD8(+) effector T cells in vivo is a critical determinant of the success of anti-tumor immunotherapy and Treg play an important role in the mechanism inhibiting the induction of multifunctionality in effector cells.
越来越明显的是，效应细胞在单细胞水平上的多功能性是预测免疫保护中T细胞反应质量的一个重要因素。然而，T细胞多功能性在抗肿瘤免疫中的意义仍不清楚。在这里，我们在单细胞水平上评估了过继转移的肿瘤抗原特异性CD8(+) T细胞中IFN-γ和TNF-α的产生以及CD107a的动员。发现小鼠纤维肉瘤CMS5的肿瘤生长限制了转移细胞中多功能性的诱导。这些细胞表现出CD25(高)GITR(高)CD62L(低)表型的获得不足以及肿瘤浸润减少。Treg的耗竭促进了即使在肿瘤进展的宿主中转移细胞的高多功能性诱导，导致肿瘤消退增强。转移细胞的多功能性与体内CTL活性相关，并且从成功治疗的宿主中收获的具有高多功能性的T细胞在重新转移到荷瘤宿主中时诱导肿瘤消退。这些数据表明，体内多功能CD8(+)效应T细胞的出现是抗肿瘤免疫治疗成功的关键决定因素，并且Treg在抑制效应细胞中多功能性诱导的机制中起重要作用。
