Poggi A, Pella N, Cantoni C, Zocchi M R, Moretta L
Laboratory of Immunopathology, Instituto Nazionale per la Ricerca sul Cancro e Centro di Biotecnologie Avanzate, Genoa, Italy.
Int Immunol. 1996 Dec;8(12):1947-53. doi: 10.1093/intimm/8.12.1947.
In this study the effects of CD45 engagement on CD3-TCR-driven stimulation of CD1+ human immature thymocytes have been analyzed. Simultaneous cross-linking of CD45 and CD3 antigens on highly purified CD1+ thymocytes reduced the number of cells undergoing apoptosis after 16 h of in vitro culture. This cell population might represent immature thymocytes committed in vivo to die by programmed cell death (PCD). CD45 engagement could also increase the number of cycling CD1+ thymocytes; of note, the large majority (> 95%) of dividing cells expressed the CD1 molecule at the cell surface, indicating that proliferating cells were actually represented by immature thymocytes. These data suggest that the CD45 molecule might play a role in the rescue of immature thymocytes from PCD during differentiation. Along this line, we found that activation of CD1+ thymocytes via the CD3-TCR complex could be enhanced by CD45, both in terms of transcription and surface expression of IL-2R. These effects might be explained by the finding that the CD45 molecule (but not its isoforms CD45RO and RA) was physically associated with the CD3-TCR complex at the cell surface of CD1+ human thymocytes, as shown by co-precipitation and co-capping experiments. Finally, cross-linking of CD45 and CD3 antigens led to the expansion of CD3+ thymocytes co-expressing CD4 and CD8, indicating that simultaneous engagement of CD45 and CD3 molecules can block CD1+ cells at the double-positive (CD3+CD4+CD8+) differentiation stage. On the other hand, stimulation through CD3 resulted in the expansion of thymocytes showing a mature phenotype (CD3+CD4+ or CD3+CD8+). Altogether, these findings suggest that the CD45 molecule is involved both in early activation and in the regulation of CD1+ thymocyte differentiation.
在本研究中，分析了CD45参与对CD3 - TCR驱动的CD1⁺人未成熟胸腺细胞刺激的影响。在高度纯化的CD1⁺胸腺细胞上同时交联CD45和CD3抗原，可减少体外培养16小时后发生凋亡的细胞数量。该细胞群体可能代表体内注定通过程序性细胞死亡（PCD）死亡的未成熟胸腺细胞。CD45的参与还可增加处于细胞周期的CD1⁺胸腺细胞数量；值得注意的是，绝大多数（>95%）正在分裂的细胞在细胞表面表达CD1分子，表明增殖细胞实际上是未成熟胸腺细胞。这些数据表明，CD45分子可能在未成熟胸腺细胞分化过程中从PCD中拯救它们的过程中发挥作用。据此，我们发现，就IL - 2R的转录和表面表达而言，CD45可增强通过CD3 - TCR复合物对CD1⁺胸腺细胞的激活。共沉淀和共封端实验表明，CD45分子（而非其异构体CD45RO和RA）在CD1⁺人胸腺细胞的细胞表面与CD3 - TCR复合物发生物理结合，这一发现或许可以解释上述效应。最后，CD45和CD3抗原的交联导致共表达CD4和CD8的CD3⁺胸腺细胞扩增，表明CD45和CD3分子的同时参与可在双阳性（CD3⁺CD4⁺CD8⁺）分化阶段阻断CD1⁺细胞。另一方面，通过CD3刺激导致呈现成熟表型（CD3⁺CD4⁺或CD3⁺CD8⁺）的胸腺细胞扩增。总之，这些发现表明，CD45分子既参与早期激活，也参与CD1⁺胸腺细胞分化的调节。
