Mojcik C F, Greiner D L, Goldschneider I
Department of Pathology, School of Medicine, University of Connecticut Health Center, Farmington 06030.
Dev Immunol. 1991;1(3):191-201. doi: 10.1155/1991/87067.
The derivation of RT6+ T cells from postthymic RT6- T cells in weanling rats was formally demonstrated by the intravenous transfer ("parking") of highly purified populations of RT6- lymph node T cells into thymectomized, irradiated, and bone-marrow-reconstituted (TXBM) RT6 and RT7 alloantigen-disparate recipients. Parallel experiments in irradiated and bone-marrow-reconstituted rats, and in rats whose RT6+ T cells had been depleted by injection of DS4.23 anti-RT6.1 mAb, suggested that the transit time between the pre-RT6+ and the RT6+ T-cell compartments approximated 4-5 days. A more precise estimate of the transit time was made by linear regression analysis of the generation of RT6+ T cells in rats that were treated with DS4.23 mAb at timed intervals after thymectomy. This study indicated that 50% of the pre-RT6+ T cells differentiated into RT6+ cells within 4 days, 75% within 8 days, and more than 90% within 16 days. Despite the apparent absence of pre-RT6- T cells 3 weeks after thymectomy, numerous RT6- T cells persisted for at least 10 weeks in thymectomized rats, even after treatment with DS4.23 mAb. Moreover, these RT6+ T cells failed to generate RT6+ T cells after transfer into adoptive hosts. Quantitative and phenotypic analyses indicated that this population of "true" RT6- T cells: (1) constitutes approximately 50% of the total RT6- T cells normally found in control rats; (2) contains CD4+ and CD8+ subsets; (3) expresses both the CD5 pan-T-cell antigen (which is absent from NK cells) and the R73 alpha/beta TCR constant-region determinant; and (4) lacks sIgM. Hence, the present results indicate that the "true" RT6- and the RT6+ T-cell subsets have stable antigenic phenotypes and represent developmentally discrete populations of postthymic cells in normal rats. This is supported by associated phenotypic and functional studies that suggest that the "true" RT6- T-cell subset contains antigenically naive and/or autoreactive clonotypes, whereas the RT6+ T-cell subset contains memory and/or regulatory cells. It remains to be determined whether the "true" RT6- and the RT6+ subsets represent separate lineages of T cells or a single lineage at different stages of activation or maturation.
通过将高度纯化的RT6 - 淋巴结T细胞群体静脉注射（“植入”）到胸腺切除、照射并骨髓重建（TXBM）的RT6和RT7同种异体抗原不同的受体中，正式证明了断奶大鼠中胸腺后RT6 - T细胞可衍生出RT6 + T细胞。在照射并骨髓重建的大鼠以及通过注射DS4.23抗RT6.1单克隆抗体使RT6 + T细胞耗竭的大鼠中进行的平行实验表明，RT6 + T细胞前体与RT6 + T细胞区室之间的过渡时间约为4 - 5天。通过对胸腺切除后按时间间隔用DS4.23单克隆抗体处理的大鼠中RT6 + T细胞生成情况进行线性回归分析，对过渡时间进行了更精确的估计。该研究表明，50%的RT6 + T细胞前体在4天内分化为RT6 + 细胞，75%在8天内分化，90%以上在16天内分化。尽管胸腺切除后3周明显不存在RT6 - T细胞前体，但在胸腺切除的大鼠中，即使在用DS4.23单克隆抗体处理后，仍有大量RT6 - T细胞持续存在至少10周。此外，这些RT6 - T细胞在转移到过继宿主后未能产生RT6 + T细胞。定量和表型分析表明，这群“真正的”RT6 - T细胞：（1）约占正常对照大鼠中总RT6 - T细胞的50%；（2）包含CD4 + 和CD8 + 亚群；（3）表达CD5泛T细胞抗原（NK细胞中不存在）和R73α/βTCR恒定区决定簇；（4）缺乏sIgM。因此，目前的结果表明，“真正的”RT6 - 和RT6 + T细胞亚群具有稳定的抗原表型，代表正常大鼠胸腺后细胞发育上离散的群体。相关的表型和功能研究支持了这一点，这些研究表明“真正的”RT6 - T细胞亚群包含抗原未致敏和/或自身反应性克隆型，而RT6 + T细胞亚群包含记忆和/或调节细胞。“真正的”RT6 - 和RT6 + 亚群是代表T细胞的不同谱系还是单个谱系在激活或成熟的不同阶段，仍有待确定。
