Fukada Kenji, Koyanagi Madoka, Arimura Yutaka, Ogiuchi Hideki, Uchiyama Takehiko, Yagi Junji
Department of Oral and Maxillofacial Surgery, Tokyo Women's Medical University School of Medicine, Tokyo, Japan.
Cell Immunol. 2005 Dec;238(2):103-12. doi: 10.1016/j.cellimm.2006.02.004. Epub 2006 Apr 4.
We previously reported that Vbeta3+ CD4+ T cells maintained a protracted expansion, with the phenotypes of memory Th2 cells, for 30 days in C57BL/6 (B6) mice implanted with SEA-containing mini-osmotic pumps. In the present study, we followed the fate of Vbeta3+ CD4+ T cells in CD28-/- mice. Vbeta3+ CD4+ T cells increased to a degree similar to that of B6 Vbeta3+ CD4+ T cells until day 10 after implantation, then declined rapidly reaching the control level by 28 days. Remaining Vbeta3+ CD4+ T cells at that time did not exhibit memory phenotypes nor Th2-deviated responses. The rapid drop in Vbeta3+ CD4+ T cells in CD28-/- mice was attributable to upregulated induction of apoptosis owing to marginal inductions of Bcl-2 and Bcl-xL. Collectively, these data indicate CD28 to play critical roles in the generation and maintenance of SEA-reactive CD4+ T cells in vivo.
我们之前报道过，在植入含SEA的微型渗透泵的C57BL/6（B6）小鼠中，Vβ3⁺ CD4⁺ T细胞维持了长达30天的持续性扩增，并具有记忆性Th2细胞的表型。在本研究中，我们追踪了CD28基因敲除小鼠中Vβ3⁺ CD4⁺ T细胞的命运。在植入后第10天之前，Vβ3⁺ CD4⁺ T细胞的增加程度与B6小鼠的Vβ3⁺ CD4⁺ T细胞相似，然后迅速下降，到28天时降至对照水平。那时剩余的Vβ3⁺ CD4⁺ T细胞既不表现出记忆表型，也没有Th2偏向性反应。CD28基因敲除小鼠中Vβ3⁺ CD4⁺ T细胞的快速下降归因于Bcl-2和Bcl-xL的诱导作用微弱，导致凋亡诱导上调。总体而言，这些数据表明CD28在体内SEA反应性CD4⁺ T细胞的产生和维持中起关键作用。
