Rakasz E, Rigby S, de Andres B, Mueller A, Hagen M, Dailey M O, Sandor M, Lynch R G
Department of Pathology, University of Iowa College of Medicine, Iowa City 52242, USA.
Int Immunol. 1998 Oct;10(10):1509-17. doi: 10.1093/intimm/10.10.1509.
The vaginal epithelium of normal mice contains lymphocytes of fetal thymic origin that express an invariant Vgamma4/Vdelta1 TCR. The apparent lack of other gammadelta TCR species suggests that a selection mechanism might operate to regulate the localization of gammadelta T cells at this anatomical site. Selection might be connected to the Vgamma4/Vdelta1 TCR or to some homing characteristic of the fetal thymic lineage that appears at day 17-18 of embryonic life. In the present studies, we investigated whether transgenic gammadelta cells expressing a TCR species characteristic of the subpopulation of gammadelta T cells found in the blood, spleen and lymph would translocate to the vaginal epithelium. We found that the transgenic Vgamma2 TCR+ cells did accumulate in the vagina of transgenic mice. Furthermore, like normal vaginal gammadelta T cells, the transgenic vaginal gammadelta T cells expressed the phenotype of recently activated memory/effector T cells (CD44(hi), CD62L-, CD45RB(lo), CD69+). Vaginal gammadelta T cells in normal mice do not express the CD2 and CD28 antigens, but both of these markers are present on transgenic vaginal gammadelta T cells. We observed that a small fraction of splenic transgenic gammadelta T cells had the same surface phenotype as the vaginal transgenic gammadelta T cells, raising the possibility that the gammadelta T cells present in the vaginal epithelium of transgenic mice originated from the peripheral lymphoid organs. Data in support of this possibility came from experiments in which co-incubation of splenic transgenic gammadelta T cells with vaginal epithelial cell suspensions induced the vaginal gammadelta phenotype on the splenic gammadelta T cells. The finding of transgenic gammadelta T cells in the vaginal epithelium suggests that homing of gammadelta T cells to this site is not restricted to gammadelta T cells that express the V4/NS1 invariant TCR. Furthermore, these findings imply that retention of gammadelta T cells in the vaginal epithelium of normal mice is affected by a Vgamma4/Vdelta1-specific mechanism. The finding of a significant level of apoptosis in the transgenic vaginal gammadelta T cells, but not in the normal vaginal gammadelta T cells, could reflect that the mechanism of retention of Vgamma4/Vdelta1 + in the vaginal epithelium involves selective survival at the site.
正常小鼠的阴道上皮含有源自胎儿胸腺的淋巴细胞，这些淋巴细胞表达恒定的Vγ4/Vδ1 TCR。明显缺乏其他γδ TCR种类表明，可能存在一种选择机制来调节γδ T细胞在这个解剖部位的定位。选择可能与Vγ4/Vδ1 TCR或胚胎生命第17 - 18天出现的胎儿胸腺谱系的某些归巢特征有关。在本研究中，我们调查了表达在血液、脾脏和淋巴结中发现的γδ T细胞亚群特征性TCR种类的转基因γδ细胞是否会转移到阴道上皮。我们发现转基因Vγ2 TCR +细胞确实在转基因小鼠的阴道中积累。此外，与正常阴道γδ T细胞一样，转基因阴道γδ T细胞表达最近激活的记忆/效应T细胞的表型（CD44(高)、CD62L -、CD45RB(低)、CD69 +）。正常小鼠的阴道γδ T细胞不表达CD2和CD28抗原，但这两种标志物都存在于转基因阴道γδ T细胞上。我们观察到一小部分脾脏转基因γδ T细胞具有与阴道转基因γδ T细胞相同的表面表型，这增加了转基因小鼠阴道上皮中存在的γδ T细胞源自外周淋巴器官的可能性。支持这种可能性的数据来自以下实验：脾脏转基因γδ T细胞与阴道上皮细胞悬液共同孵育可诱导脾脏γδ T细胞出现阴道γδ表型。在阴道上皮中发现转基因γδ T细胞表明，γδ T细胞归巢到这个部位并不局限于表达V4/NS1恒定TCR的γδ T细胞。此外，这些发现意味着正常小鼠阴道上皮中γδ T细胞的保留受Vγ4/Vδ1特异性机制影响。在转基因阴道γδ T细胞中发现有显著水平的凋亡，但正常阴道γδ T细胞中没有，这可能反映出Vγ4/Vδ1 +在阴道上皮中的保留机制涉及该部位的选择性存活。
