Kosaka Akemi, Wakita Daiko, Matsubara Naoki, Togashi Yuji, Nishimura Shin-Ichiro, Kitamura Hidemitsu, Nishimura Takashi
Division of Immunoregulation, Section of Disease Control, Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan.
Int Immunol. 2007 Mar;19(3):249-56. doi: 10.1093/intimm/dxl140. Epub 2007 Jan 17.
In unimmunized specific pathogen-free mice, there are unique memory-type CD8(+) T cell populations expressing asialoGM1 (ASGM1). These cells were classified into central memory-type T cells (T(CMT)) judging from their expression profile of CD44, IL-2Rbeta, CD62L and CCR7 cell-surface molecules. Among CD44(high)CD8(+) so-called memory CD8(+) T cell population, ASGM1(+)CD44(high)CD8(+) T(CMT), but not ASGM1(-)CD44(high)CD8(+) memory T cells, produced IFN-gamma by stimulation with anti-CD3 mAb. The physiological significance of ASGM1(+)CD8(+) T(CMT) as early source of IFN-gamma was also demonstrated in vivo. Namely, intravenous injection of anti-CD3 mAb (2 microg) resulted in early activation of IFN-gamma-producing ASGM1(+)CD8(+) T(CMT) cells as well as NKT and NK cells. Unexpectedly, however, few IFN-gamma-producing CD4(+) T cells were detected until 4 h after anti-CD3 mAb administration. Thus, ASGM1(+)CD8(+) T(CMT) were demonstrated to be early IFN-gamma producer, which may be crucial for T(h)1-dependent cellular immunity. Indeed, co-culture of naive CD4(+) T cells with ASGM1(+)CD8(+) T(CMT) but not ASGM1(-)CD8(+) T cells caused a great acceleration of IFN-gamma-producing T(h)1 cells in vitro. Finally, we found that T(h)1-prone C57BL/6 mice possessed higher percentage (10%) of ASGM1(+)CD8(+) T(CMT) in CD8(+) T cells compared with that (3%) of T(h)2-prone BALB/c mice. Moreover, ASGM1(+)CD8(+) T(CMT) derived from C57BL/6 mice produced higher levels of IFN-gamma compared with those from BALB/c mice. Thus, ASGM1(+)CD8(+) T(CMT), whose differentiation in vivo is genetically controlled, appear to play a critical role in the control of type 1 immunity, which is essential for therapy of tumors and infectious diseases.
在未免疫的无特定病原体小鼠中，存在表达去唾液酸GM1（ASGM1）的独特记忆型CD8(+) T细胞群体。根据这些细胞表面分子CD44、IL-2Rβ、CD62L和CCR7的表达谱，将这些细胞分类为中枢记忆型T细胞（T(CMT)）。在CD44(高)CD8(+)所谓的记忆CD8(+) T细胞群体中，ASGM1(+)CD44(高)CD8(+) T(CMT)，而非ASGM1(-)CD44(高)CD8(+)记忆T细胞，在抗CD3单克隆抗体刺激下产生干扰素-γ。ASGM1(+)CD8(+) T(CMT)作为干扰素-γ早期来源的生理意义在体内也得到了证实。即静脉注射抗CD3单克隆抗体（2微克）导致产生干扰素-γ的ASGM1(+)CD8(+) T(CMT)细胞以及NKT和NK细胞的早期激活。然而，出乎意料的是，在抗CD3单克隆抗体给药后4小时之前，几乎检测不到产生干扰素-γ的CD4(+) T细胞。因此，ASGM1(+)CD8(+) T(CMT)被证明是早期干扰素-γ产生者，这可能对Th1依赖性细胞免疫至关重要。实际上，在体外，幼稚CD4(+) T细胞与ASGM1(+)CD8(+) T(CMT)而非ASGM1(-)CD8(+) T细胞共培养导致产生干扰素-γ的Th1细胞显著加速。最后，我们发现倾向于Th1的C57BL/6小鼠在CD8(+) T细胞中ASGM1(+)CD8(+) T(CMT)的百分比（10%）高于倾向于Th2的BALB/c小鼠（3%）。此外，源自C57BL/6小鼠的ASGM1(+)CD8(+) T(CMT)产生的干扰素-γ水平高于源自BALB/c小鼠的。因此，其体内分化受基因控制的ASGM1(+)CD8(+) T(CMT)似乎在1型免疫控制中起关键作用，这对肿瘤和传染病治疗至关重要。
