Analyses of T Cell Proliferation/Differentiation and Repertoire Selection in the thy Usus

新建立的胸腺基质细胞克隆MRL104.8a具有表达Ia抗原的能力，并支持抗原特异性的白介素2(IL-2)依赖的辅助性T细胞(Th)克隆的生长，而不需要抗原和外源性IL-2。这一基质细胞克隆的单层显示了维持未成熟双阴性胸腺细胞的能力。这种能力也由MRL104.8a单层产生的一个因子来表示。该因子被命名为胸腺基质衍生T细胞生长因子(TSTGF)，与IL-2或IL-4不同，但在功能和分子水平上与上述细胞因子中的IL-7相似。MRL104.8a单层对双阴性胸腺细胞也有促分化作用。纯化的双阴性胸腺细胞在单层上培养1d，可诱导出相当比例的CD348细胞。这种分化也可以由半纯裂的TSTGF样本诱导，但n…提示MRL104.8a细胞除与IL-7相同或密切相关的促生长因子外，还分泌一种启动双阴性细胞分化的因子(S)。当双阴性胸腺细胞的培养周期延长到2或3天时，在MRL104.8a单层上产生了相当数量的双阳性细胞(CD4^+8^+)和单阳性细胞(CD4^+8^-)。这些数据还表明，我们的胸腺基质细胞可能与胸腺的克隆消除有关。在缺乏Th克隆所针对的抗原的情况下，Th克隆9-16的生长依赖于产生TSTGF和表达la的MRL104.8a单层。相反，MRL104.8a培养物中相关抗原的存在可引起Th克隆细胞的致死性生长抑制。因此，这些观察结果有力地支持了这样的命题，即在T细胞生长和分化以及T细胞谱系选择的背景下，特化的胸腺基质成分在胸腺内T细胞的发育中起着至关重要的作用。较少

A newly established thymic stromal cell clone, MRL104.8a exhibited capacities to express Ia antigens and to support the growth of antigenspecific, interleukin-2 (IL-2) -dependent helper T cell (Th) clones without requirement of antigen and exogenous IL-2. The monolayer of this stromal cell clone exhbited the capacity to maintain immature double-negative thymocytes. Such capacity was also expressed by a factor produced by the MRL104.8a monolayer. This factor designated as Thymic Stroma-derived T cell Growth Factor (TSTGF) was found to be distinct from IL-2 or IL-4 but similar to IL-7 of the previously described cytokines from the functional and molecular aspects. The MRL104.8a monolayer also exerted its defferentiation-promoting effect on double-negative thymocytes. Culture for one day of purified double-negative thymocytes on the monolayer resulted in the induction of an appreciable percent of CD3 4 8 cells. This differentiation could also be induced by a semipurifid TSTGF sample but n … More ot by recombinant IL-7, suggesting that the MRL104.8a cells elaborate a factor (s) responsible for initiating the differentiation of doublenegative cells in addition to the growth-promotion factor identical or closely related to IL-7. When the culture period of double-negative thymocytes was extended to 2 or 3 days, an appreciable number of doublepositive (CD4^+8^+) and single-positive (CD4^+8^-) cells were generated on the MRL104.8a monolayer. The data were also presented that our thymic stromal cells could coutribute to the clonal elimination in the thymus. The growth of a Th clone, 9-16, was supported on the TSTGF-producing and la-expressing MRL104.8a monolayer in the absence of the antigen against which this Th clone is directed. In contrast, the presence ofthe relevant antigen in the MRL104.8a culture elicited the lethal growth-inhibition of Th clone cells. Thus, these observations provide strong support for the proposition that a specialized thymic stromal component plays an essetial role in the intrathymic T cell development in the context of T cell growth and differentiation as well as T cell repertoire selection. Less