Offner F, Van Beneden K, Debacker V, Vanhecke D, Vandekerckhove B, Plum J, Leclercq G
Department of Clinical Chemistry, Microbiology, and Immunology, University of Ghent, University Hospital, Belgium.
J Immunol. 1997 May 15;158(10):4634-41.
In contrast to thymic differentiation of TCR alphabeta cells, differentiation stages of TCR gammadelta cells are largely unknown. This report shows that CD1, a known marker of immature TCR alphabeta thymocytes, was expressed on some postnatal TCR gammadelta thymocytes. Only CD1+ TCR gammadelta thymocytes expressed recombination-activating gene-1 mRNA, and they were shown to differentiate into CD1- TCR gammadelta thymocytes. Functionally, sorted CD1- TCR gammadelta thymocytes proliferated in the presence of immobilized anti-CD3 Ab plus exogenous rIL-2 or rIL-15. Interestingly, in contrast to CD1- TCR alphabeta cells, CD1- TCR gammadelta thymocytes also proliferated extensively when cultured with exogenous rIL-2 or rIL-15 alone. FACS analysis as well as reverse transcription-PCR analysis showed that only CD1- TCR gammadelta thymocytes expressed IL-2Rbeta protein and mRNA. The differential expression of maturation markers, such as CD27, CD45RO, and CD45RA, as a function of expression of CD1 was similar in TCR gammadelta and TCR alphabeta thymocytes. An important exception is the expression of CD4 and CD8. Whereas TCR alphabeta thymocytes are mainly CD4-CD8 double positive at the immature CD1+ stage and CD4 or CD8 single positive at the mature CD1- stage, CD1(bright) TCR gammadelta thymocytes all expressed CD4, but only some of them expressed CD8. Some CD1- TCR gammadelta thymocytes also expressed CD8, but were negative for CD4. Collectively, our data clearly show that CD1 is a useful marker to distinguish immature human TCR gammadelta thymocytes from functional mature gammadelta cells based on recombination-activating gene-1 expression, in vitro differentiation, and phenotypic and functional characteristics.
与TCRαβ细胞的胸腺分化不同，TCRγδ细胞的分化阶段在很大程度上尚不清楚。本报告显示，CD1是未成熟TCRαβ胸腺细胞的已知标志物，在一些出生后的TCRγδ胸腺细胞上表达。只有CD1+TCRγδ胸腺细胞表达重组激活基因-1mRNA，并且它们被证明可分化为CD1-TCRγδ胸腺细胞。在功能上，分选的CD1-TCRγδ胸腺细胞在固定化抗CD3抗体加外源性rIL-2或rIL-15存在的情况下增殖。有趣的是，与CD1-TCRαβ细胞不同，CD1-TCRγδ胸腺细胞单独用外源性rIL-2或rIL-15培养时也能大量增殖。流式细胞术分析以及逆转录-PCR分析表明，只有CD1-TCRγδ胸腺细胞表达IL-2Rβ蛋白和mRNA。作为CD1表达的函数，成熟标志物如CD27、CD45RO和CD45RA的差异表达在TCRγδ和TCRαβ胸腺细胞中相似。一个重要的例外是CD4和CD8的表达。虽然TCRαβ胸腺细胞在未成熟的CD1+阶段主要是CD4-CD8双阳性，在成熟的CD1-阶段是CD4或CD8单阳性，但CD1(明亮)TCRγδ胸腺细胞都表达CD4，但只有其中一些表达CD8。一些CD1-TCRγδ胸腺细胞也表达CD8，但CD4为阴性。总体而言，我们的数据清楚地表明，基于重组激活基因-1表达、体外分化以及表型和功能特征，CD1是区分未成熟人类TCRγδ胸腺细胞与功能性成熟γδ细胞的有用标志物。
