Hargreaves M, Bell E B
Immunology Research Group, Medical School, University of Manchester, UK.
Immunology. 1997 Jul;91(3):323-30. doi: 10.1046/j.1365-2567.1997.00267.x.
Naive and memory CD4 T cells are frequently defined by exon-specific monoclonal antibodies (mAb) which stain (or not) high- or low-molecular-weight (MW) isoforms of the leucocyte common antigen CD45. The link between isoform and the naive/memory designation is complicated by the fact that CD4 T cells with a 'memory' phenotype (CD45RA-, RB-, RC-, or CD45RO+) may revert ('revertants') and re-express the high mw isoform (CD45RA+, RB+, RC+). Isoform expression also changes during normal T-cell development. Furthermore, the picture may be incomplete since an exon-specific mAb will not detect all possible isoforms on a cell. We have used molecular techniques to determine whether revertant CD4 memory T cells were different from naive T cells with respect to CD45R isoform expression. Using the anti-CD45RC mAb OX22 to purify rat lymphocyte subsets, CD45R isoform expression was examined at the mRNA level in CD4 T cells at different stages of development and compared with that of B cells and unseparated lymphocytes. B cells contained abundant message for the highest MW 3-exon isoform ABC, the 2-exon isoforms AB and BC, and the null isoform O. Both immature CD45RC- (i.e. CD4+8- 'single positive' thymocytes, and peripheral Thy-1+ recent thymic emigrants) and mature CD45RC- 'antigen-experienced' CD4 T cells had message for single-exons B, possibly C and for the O exon. In contrast, CD45RC+ CD4 T cells contained mRNA coding for ABC (low level), AB, BC, B, C (low level) and O (low level). Importantly, there was no difference between CD45RC+ T cells that had not seen antigen ('truly native') and CD45RC+ antigen-experienced revertant memory T cells. This observation has implications for understanding long-term immunological memory.
初始和记忆性CD4 T细胞通常由外显子特异性单克隆抗体（mAb）来定义，这些抗体可对白细胞共同抗原CD45的高分子量（MW）或低分子量异构体进行染色（或不染色）。异构体与初始/记忆性分类之间的联系较为复杂，因为具有“记忆”表型（CD45RA-、RB-、RC-或CD45RO+）的CD4 T细胞可能会发生逆转（“逆转细胞”）并重新表达高分子量异构体（CD45RA+、RB+、RC+）。异构体表达在正常T细胞发育过程中也会发生变化。此外，由于外显子特异性mAb无法检测细胞上所有可能的异构体，情况可能并不完整。我们使用分子技术来确定逆转的CD4记忆T细胞在CD45R异构体表达方面是否与初始T细胞不同。利用抗CD45RC mAb OX22纯化大鼠淋巴细胞亚群，在不同发育阶段的CD4 T细胞中检测CD45R异构体在mRNA水平的表达，并与B细胞和未分离的淋巴细胞进行比较。B细胞含有丰富的最高分子量3外显子异构体ABC、2外显子异构体AB和BC以及零异构体O的信息。未成熟的CD45RC-（即CD4+8-“单阳性”胸腺细胞和外周Thy-1+近期胸腺迁出细胞）和成熟的CD45RC-“抗原接触过的”CD4 T细胞都含有单外显子B、可能还有C以及O外显子的信息。相比之下，CD45RC+ CD4 T细胞含有编码ABC（低水平）、AB、BC、B、C（低水平）和O（低水平）的mRNA。重要的是，未接触过抗原的CD45RC+ T细胞（“真正的初始细胞”）与经历过抗原的CD45RC+逆转记忆T细胞之间没有差异。这一观察结果对于理解长期免疫记忆具有重要意义。
