Reichert R A, Jerabek L, Gallatin W M, Butcher E C, Weissman I L
J Immunol. 1986 May 15;136(10):3535-42.
The monoclonal antibody MEL-14 has been used in conjunction with immunohistology and multiparameter immunofluorescence to identify and characterize homing receptor-bearing thymocytes at various stages of embryonic and neonatal development. MEL-14hi thymocytes first appear at day 14 of gestation and come to represent about 40% of day 15 fetal thymocytes. Thereafter, the proportion of MEL-14hi thymocytes rapidly declines such that by birth (usually the 20th day of embryonic development) only about 2% of thymocytes are MEL-14hi. Although newborn thymocytes resemble adult thymocytes in this respect, the phenotypic characteristics of fetal and neonatal MEL-14hi thymocytes suggest that this unique subset undergoes a gradual transition from containing exclusively phenotypically immature cells in early gestation to containing predominantly phenotypically mature cells by young adulthood. Thus, virtually none of day 15 MEL-14hi fetal thymocytes are peanut agglutinin (PNA)lo, Ly-1hi, or either Lyt-2-/L3T4+ or Lyt-2+/L3T4-, whereas in the weeks that follow a steadily greater proportion of MEL-14hi thymocytes come to express this mature pattern (roughly 70% at 4 wk of age). Most day 15 MEL-14hi fetal thymocytes appear to express the functional homing receptor molecule, since day 15 fetal thymocytes bind to peripheral lymph node high endothelial venules about 40 to 50% as well as do adult mesenteric node lymphocytes, whereas adult thymocytes bind only about 5% as well. We have also identified a population of outer cortical MEL-14hi Lyt-2-/L3T4- lymphoblasts that appears during thymus regeneration 5 to 6 days after the administration of hydrocortisone. These lymphoblasts express the same phenotype as cells that constitute 40% of the day 15 fetal thymus and only 0.4% of normal adult thymocytes, implying that this particular subset may make up a significant fraction of thymocytes whenever there is a requirement for rapid expansion of the intrathymic and/or peripheral T cell pools. Taken together, these results are consistent with the notion that expression of the MEL-14-defined homing receptor may be closely linked to important intrathymic events that may occur early in T cell development and yet still have an overriding impact on the selection of those thymocytes that will serve as precursors of thymus emigrants.
单克隆抗体MEL-14已与免疫组织学和多参数免疫荧光结合使用，以鉴定和表征在胚胎和新生儿发育的各个阶段带有归巢受体的胸腺细胞。MEL-14高表达的胸腺细胞最早出现在妊娠第14天，约占第15天胎儿胸腺细胞的40%。此后，MEL-14高表达的胸腺细胞比例迅速下降，以至于到出生时（通常是胚胎发育的第20天），只有约2%的胸腺细胞是MEL-14高表达的细胞。尽管新生儿胸腺细胞在这方面与成年胸腺细胞相似，但胎儿和新生儿MEL-14高表达的胸腺细胞的表型特征表明，这个独特的亚群经历了一个逐渐的转变，从妊娠早期仅含有表型不成熟的细胞，到成年早期主要含有表型成熟的细胞。因此，实际上第15天的MEL-14高表达的胎儿胸腺细胞中没有花生凝集素（PNA）低表达、Ly-1高表达，或Lyt-2-/L3T4+或Lyt-2+/L3T4-的细胞，而在接下来的几周里，越来越多比例的MEL-14高表达的胸腺细胞开始表达这种成熟模式（4周龄时约为70%）。大多数第15天的MEL-14高表达的胎儿胸腺细胞似乎表达功能性归巢受体分子，因为第15天的胎儿胸腺细胞与外周淋巴结高内皮微静脉的结合能力约为成年肠系膜淋巴结淋巴细胞的40%至50%，而成年胸腺细胞的结合能力仅约为5%。我们还鉴定出一群皮质外层的MEL-14高表达、Lyt-2-/L3T4-的淋巴母细胞，它们在给予氢化可的松后5至6天的胸腺再生过程中出现。这些淋巴母细胞表达的表型与构成第15天胎儿胸腺40%、正常成年胸腺细胞仅0.4%的细胞相同，这意味着每当需要快速扩大胸腺内和/或外周T细胞库时，这个特定的亚群可能构成胸腺细胞的很大一部分。综上所述，这些结果与以下观点一致，即MEL-14定义的归巢受体的表达可能与T细胞发育早期可能发生的重要胸腺内事件密切相关，并且对那些将作为胸腺迁出细胞前体的胸腺细胞的选择仍有首要影响。
