AsialoGM1+CD8+ central memory-type T cells in unimmunized mice as novel immunomodulator of IFN-γ-dependent type 1 immunity
AsialoGM1+CD8+ central memory-type T cells in unimmunized mice as novel immunomodulator of IFN-γ-dependent type 1 immunity
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DOI：
10.1093/intimm/dxl140
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发表时间：
2007-03-01
影响因子：
4.4
通讯作者：
Nishimura, Takashi
中科院分区：
文献类型：
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作者：
Kosaka, Akemi;Wakita, Daiko;Nishimura, Takashi
在未免疫的无特定病原体小鼠中，存在表达无唾液酸GM 1（ASGM 1）的独特记忆型CD 8（+）T细胞群。根据CD 44、IL-2 R β、CD 62 L和CCR 7细胞表面分子的表达谱将这些细胞分类为中央记忆型T细胞（T-CMT）。在CD 44（高）CD 8（+）所谓的记忆CD 8（+）T细胞群中，ASGM 1（+）CD 44（高）CD 8（+）T-CMT，但ASGM 1（-）CD 44（高）CD 8（+）记忆T细胞不会通过抗CD 3 mAb刺激产生IFN-γ。ASGM 1（+）CD 8（+）T-CMT作为IFN-γ的早期来源的生理意义也在体内得到证实。即，静脉注射抗CD 3 mAb（2 μ g）导致产生IFN-γ的ASGM 1（+）CD 8（+）T-CMT细胞以及NKT和NK细胞的早期活化。然而，出乎意料的是，直到抗CD 3 mAb给药后4 h才检测到少量产生IFN-γ的CD 4（+）T细胞。因此，ASGM 1（+）CD 8（+）T-CMT被证明是早期IFN-γ产生者，这可能对T（h）1依赖性细胞免疫至关重要。事实上，初始CD 4（+）T细胞与ASGM 1（+）CD 8（+）T-CMT而非ASGM 1（-）CD 8（+）T细胞的共培养在体外引起产生IFN-γ的T（h）1细胞的极大加速。最后，我们发现T（h）1倾向的C57 BL/6小鼠的ASGM 1（+）CD 8（+）T-CMT在CD 8（+）T细胞中的百分比（10%）高于T（h）2倾向的BALB/c小鼠（3%）。此外，来自C57 BL/6小鼠的ASGM 1（+）CD 8（+）T-CMT产生的IFN-γ水平高于来自BALB/c小鼠的那些。因此，ASGM 1（+）CD 8（+）T-CMT在体内的分化是受遗传控制的，似乎在控制1型免疫中发挥关键作用，这对于肿瘤和感染性疾病的治疗是必不可少的。
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-2R beta, 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 mu g) 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.