Lee C K, Kim K, Welniak L A, Murphy W J, Muegge K, Durum S K
Laboratory of Molecular Immunoregulation, Division of Basic Sciences, National Cancer Institute and Intramural Research Support Program, Science Application International Corporation, Frederick, MD 21702-1201, USA.
Blood. 2001 Mar 1;97(5):1360-9. doi: 10.1182/blood.v97.5.1360.
T cells that emigrate from the thymus have primarily been studied in vivo using fluorescent dye injection of the thymus. This study examined the properties of thymocytes that emigrate from cultured thymic lobes in organ culture. Under these conditions, thymic emigrants displayed the expected phenotype, that of mature thymocytes expressing high levels of T-cell receptor (TCR-alphabeta) and either CD4 or CD8, and were observed to emigrate within 24 hours of positive selection. Emigration was inhibited by cytochalasin D, pertussis toxin, or Clostridium difficile toxin B, implicating an active motility process. Most of the surface markers on alphabeta-thymic emigrants (Thy1, CD44, CD69, CD25, leukocyte functional antigen-1, intercellular adhesion molecule-1, alpha(4)-integrin, alpha(5)-integrin, CD45, and CD28) were expressed at a surface density similar to that on mature intrathymic cells and peripheral splenic T cells. Heterogeneous expression of L-selectin and heat-stable antigen (HSA) suggested that subsets emerge from the thymus with a commitment to different migration patterns. The only marker on emigrants not found on either intrathymic cells or mature spleen T cells was CTLA-4, which could dampen the response of emigrants to peripheral antigens. Antigen responsivenes measured in vitro against allogeneic dendritic cells showed a proliferative response comparable to that of splenic T cells. In vivo, however, thymic emigrants failed to induce an acute graft-versus-host reaction in allogeneic severe combined immunodeficiency recipients. This suggests that a mechanism operating in vivo, perhaps tolerance or migration pattern, attenuates the response of emigrants against antigens that did not induce their deletion in the thymus.
从胸腺迁出的T细胞主要是在体内通过向胸腺注射荧光染料进行研究的。本研究检测了在器官培养中从培养的胸腺叶迁出的胸腺细胞的特性。在这些条件下，胸腺迁出细胞表现出预期的表型，即表达高水平T细胞受体（TCR-αβ）以及CD4或CD8的成熟胸腺细胞的表型，并且观察到它们在阳性选择后24小时内迁出。细胞松弛素D、百日咳毒素或艰难梭菌毒素B可抑制迁出，这表明存在一个活跃的迁移过程。αβ-胸腺迁出细胞上的大多数表面标志物（Thy1、CD44、CD69、CD25、白细胞功能抗原-1、细胞间黏附分子-1、α4整合素、α5整合素、CD45和CD28）的表面密度与成熟的胸腺内细胞和外周脾T细胞上的相似。L-选择素和热稳定抗原（HSA）的异质性表达表明，从胸腺中出现了具有不同迁移模式倾向的亚群。迁出细胞上唯一在胸腺内细胞或成熟脾T细胞上未发现的标志物是CTLA-4，它可抑制迁出细胞对外周抗原的反应。体外针对同种异体树突状细胞测量的抗原反应性显示出与脾T细胞相当的增殖反应。然而，在体内，胸腺迁出细胞未能在同种异体严重联合免疫缺陷受体中诱导急性移植物抗宿主反应。这表明在体内起作用的一种机制，可能是耐受性或迁移模式，减弱了迁出细胞对在胸腺中未诱导其缺失的抗原的反应。
