Preffer F I, Kim C W, Fischer K H, Sabga E M, Kradin R L, Colvin R B
Immunopathology Unit, Department of Pathology, Massachusetts General Hospital Boston, Massachusetts.
J Exp Med. 1989 Jul 1;170(1):177-90. doi: 10.1084/jem.170.1.177.
CD7+CD3- cells purified (greater than 99.99%) by FACS from the peripheral blood of healthy adults include precursors for mature T cells that have the capacity to differentiate into TCR-1+ or TCR-2+ CD3+ cells. Extrathymic differentiation was demonstrable from all eight healthy donors in the presence of a high concentration of IL-2, mitogenic levels of PHA, and irradiated blood mononuclear feeder cells, after a lag of approximately 40 d in vitro. The extrathymic T (ET) cells were predominantly TCR-1+, although TCR-2+ cells were also derived. ET TCR-1+ cells were CD4-CD8-, CD4-CD8DIM+, and CD4+CD8-, and were distinguished from natural T TCR-2+ cells by a variety of cell surface markers. The ET cells had phenotypes generally displayed by normal mature T cells, although the CD5DIM+ on ET cells was more typical of thymocytes. Acquisition of CD3 on purified CD7+CD3- cells was not due to antigenic modulation or growth of contaminants, and ET cells could be demonstrated at the clonal level. Studies in athymic mice and bone marrow recipients support the view that extrathymic maturation does occur in vivo. Whether the CD7+CD3- cell population was unexposed to the thymus, or exposed but not processed, is unknown. In any case, unusual or "forbidden" autoreactive specificities are predicted since ET cells differentiate without thymic selection of the TCR.
通过荧光激活细胞分选术（FACS）从健康成年人外周血中纯化（纯度大于99.99%）得到的CD7⁺CD3⁻细胞包含成熟T细胞的前体细胞，这些前体细胞有能力分化为TCR-1⁺或TCR-2⁺CD3⁺细胞。在高浓度白细胞介素-2、促有丝分裂水平的植物血凝素（PHA）以及经辐照的血液单核饲养细胞存在的情况下，体外培养约40天的延迟期后，来自所有8名健康供体的胸腺外分化均可得到证实。胸腺外T（ET）细胞主要为TCR-1⁺，不过也可衍生出TCR-2⁺细胞。ET TCR-1⁺细胞为CD4⁻CD8⁻、CD4⁻CD8DIM⁺和CD4⁺CD8⁻，并通过多种细胞表面标志物与天然T TCR-2⁺细胞相区分。ET细胞具有正常成熟T细胞通常表现出的表型，尽管ET细胞上的CD5DIM⁺更具胸腺细胞的典型特征。纯化的CD7⁺CD3⁻细胞上CD3的获得并非由于抗原调节或污染物生长，并且可在克隆水平证实ET细胞的存在。对无胸腺小鼠和骨髓受体的研究支持胸腺外成熟确实在体内发生这一观点。CD7⁺CD3⁻细胞群体是未接触胸腺，还是接触了但未经过处理，尚不清楚。无论如何，由于ET细胞在没有TCR胸腺选择的情况下分化，预计会出现异常或“禁忌”的自身反应性特异性。
