Lepique Ana Paula, Palencia Sharina, Irjala Heikki, Petrie Howard T
Memorial Sloan-Kettering Cancer Center, Box 341, 1275 York Avenue, New York, NY 10021, USA.
Clin Dev Immunol. 2003 Mar;10(1):27-33. doi: 10.1080/10446670310001598492.
T cell progenitors derive from the bone marrow but must migrate via bloodstream to the thymus in order to differentiate. The mechanism by which the thymus recruits progenitors from the blood is unknown. It is known, however, that there are receptive and refractory periods for progenitor recruitment and that when cells are imported, they enter the thymus through post-capillary venules. Therefore, recruitment is an active process temporally and spatially regulated. In order to characterize the mechanism of recruitment, we evaluated vascular signals known to regulate leukocyte extravasation, with respect to their intrathymic location and temporal fluctuations. We find that CD34, MECA79, VCAM-1, ICAM-1 and VAP-1 are all expressed in thymic blood vessels. MECA79 and VAP-1 appear to be specific for post-capillary venules, while ICAM-1 and VCAM-1 are also found on intrathymic stromal cells. MAdCAM is also expressed in the thymus, but is not associated with vascular tissues. Only MECA79 is upregulated during recruitment peaks, suggesting a role for this molecule in the periodicity of recruitment. Together, these studies reveal potential roles for L-selectin ligands, VCAM-1, ICAM-1 and VAP-1 in progenitor recruitment to the thymus, and implicate the presence of other periodic signals, such as chemokines and cytokines, that cooperate to execute this essential function.
T细胞祖细胞来源于骨髓,但必须通过血液循环迁移至胸腺才能分化。胸腺从血液中招募祖细胞的机制尚不清楚。然而,已知祖细胞招募存在接受期和不应期,并且当细胞被输入时,它们通过毛细血管后微静脉进入胸腺。因此,招募是一个在时间和空间上受到调控的活跃过程。为了阐明招募机制,我们评估了已知调控白细胞外渗的血管信号,包括它们在胸腺内的位置和时间波动情况。我们发现CD34、MECA79、VCAM - 1、ICAM - 1和VAP - 1均在胸腺血管中表达。MECA79和VAP - 1似乎对毛细血管后微静脉具有特异性,而ICAM - 1和VCAM - 1也存在于胸腺基质细胞上。MAdCAM也在胸腺中表达,但与血管组织无关。仅MECA79在招募高峰期上调,表明该分子在招募的周期性中发挥作用。总之,这些研究揭示了L - 选择素配体、VCAM - 1、ICAM - 1和VAP - 1在祖细胞向胸腺招募中的潜在作用,并暗示存在其他周期性信号,如趋化因子和细胞因子,它们共同协作执行这一重要功能。