Crompton T, Ohashi P, Schneider S D, Pircher H, MacDonald H R
Ludwig Institute for Cancer Research, Lausanne Branch, Epalinges, Switzerland.
Int Immunol. 1992 Feb;4(2):153-61. doi: 10.1093/intimm/4.2.153.
Two populations of CD4 single positive (SP) thymocytes were found in transgenic mice bearing class I-restricted Mls-1a reactive (V beta 8.1) TCR genes in the absence of the restriction element. CD3high CD4 SP cells were deleted in the presence of Mls-1a and were cortisone resistant, whereas CD3low CD4 SP cells were not deleted in the presence of Mls-1a and were cortisone sensitive. Intravenous transfer of CD3low CD4 SP cells into nude mice resulted in significant peripheral expansion of these cells with apparent upregulation of CD3. These data indicate that CD3low CD4 SP thymocytes represent an intermediate stage in the transition from CD3low double positive (DP) to CD3high SP thymocytes and raise the possibility that these cells may hve undergone positive but not negative selection events (at least to Mls-1a). Furthermore the fact that CD3high DP thymocytes were also deleted by Mls-1a in these mice suggests strongly that sensitivity to Mls-1a deletion is dependent upon stage of thymic maturation (as revealed by TCR density) rather than CD4/CD8 phenotype.
在缺乏限制元件的情况下,在携带I类限制性Mls-1a反应性(Vβ8.1)TCR基因的转基因小鼠中发现了两群CD4单阳性(SP)胸腺细胞。在存在Mls-1a的情况下,CD3高表达的CD4 SP细胞被清除且对可的松有抗性,而CD3低表达的CD4 SP细胞在存在Mls-1a的情况下未被清除且对可的松敏感。将CD3低表达的CD4 SP细胞静脉注射到裸鼠体内导致这些细胞在周围显著扩增,且CD3明显上调。这些数据表明,CD3低表达的CD4 SP胸腺细胞代表了从CD3低表达的双阳性(DP)胸腺细胞向CD3高表达的SP胸腺细胞转变的中间阶段,并增加了这些细胞可能经历了阳性而非阴性选择事件(至少对Mls-1a)的可能性。此外,在这些小鼠中CD3高表达的DP胸腺细胞也被Mls-1a清除这一事实强烈表明,对Mls-1a清除的敏感性取决于胸腺成熟阶段(如通过TCR密度所揭示)而非CD4/CD8表型。