Haas W, Pereira P, Tonegawa S
Hoffman-LaRoche, Inc., Nutley, New Jersey 07110.
Annu Rev Immunol. 1993;11:637-85. doi: 10.1146/annurev.iy.11.040193.003225.
Before TCR rearrangements, T cell progenitors are committed not only to the alpha beta and gamma delta T cell lineage but also to various subsets of both lineages. In the mouse, distinct gamma delta T cell subsets can develop in the fetal thymus, the adult thymus, or independently of a thymus, probably in intestinal epithelia. The two subsets that develop in the fetal thymus home to and are maintained throughout adult life in the skin and the mucosa of the uterus, vagina, and tongue. They are monospecific. This unusual restriction in receptor repertoires is the result of severe limitations in the generation of diversity in the fetal progenitors of these subsets and the thymic selection. After birth, one gamma delta T cell subset appears in the blood, spleen, and lymph nodes and one in the intestinal epithelia. The receptor repertoires of these subsets are characterized by the preferential usage of particular V gamma gene segments and extensive junctional diversity. Several murine and human gamma delta T cell clones have been shown to recognize classical MHC class I and class II proteins or MHC class I-like proteins, and in very few cases the presented peptides are known. We suspect that the various murine gamma delta T cell subsets interact with different antigen presenting cells which utilize different antigen presenting proteins and reside in different tissues. The function of gamma delta T cells remains unknown. Preliminary results of experiments with gene knock out mice which lack either alpha beta T cells or gamma delta T cells or both suggest that gamma delta T cells do not function as helper cells in humoral immune responses but may complement alpha beta T cells in the defense against various microorganisms.
在T细胞受体重排之前,T细胞祖细胞不仅定向分化为αβ和γδ T细胞谱系,还定向分化为这两个谱系的各种亚群。在小鼠中,不同的γδ T细胞亚群可在胎儿胸腺、成年胸腺中发育,或独立于胸腺发育,可能在肠道上皮中发育。在胎儿胸腺中发育的两个亚群归巢至皮肤以及子宫、阴道和舌的黏膜,并在成年期维持存在。它们是单特异性的。这些受体库的这种不寻常限制是这些亚群的胎儿祖细胞多样性产生以及胸腺选择受到严重限制的结果。出生后,一个γδ T细胞亚群出现在血液、脾脏和淋巴结中,另一个出现在肠道上皮中。这些亚群的受体库的特征在于特定Vγ基因片段的优先使用和广泛的连接多样性。已经证明,一些小鼠和人类γδ T细胞克隆可识别经典的MHC I类和II类蛋白或MHC I类样蛋白,在极少数情况下,所呈递的肽是已知的。我们怀疑各种小鼠γδ T细胞亚群与不同的抗原呈递细胞相互作用,这些抗原呈递细胞利用不同的抗原呈递蛋白并存在于不同的组织中。γδ T细胞的功能仍然未知。对缺乏αβ T细胞或γδ T细胞或两者的基因敲除小鼠进行实验的初步结果表明,γδ T细胞在体液免疫反应中不作为辅助细胞发挥作用,但可能在抵御各种微生物方面补充αβ T细胞。