Ying Xiaoyan, Chan Kee, Shenoy Priti, Hill Myriam, Ruddle Nancy H
Yale University School of Medicine, Department of Epidemiology and Public Health, 60 College St., P.O. Box 208034, New Haven, CT 06520-8034, USA.
Am J Pathol. 2005 Jan;166(1):135-46. doi: 10.1016/S0002-9440(10)62239-0.
The mechanism of nasal-associated lymphoid tissue (NALT) development is incompletely understood with regard to the roles of cytokines, chemokines, and vascular addressins. Development of the wild-type NALT continued in the immediate postnatal period with gradual increases in cellularity, compartmentalization into T- and B-cell zones, and expression of lymphotoxin (LT)-alpha, LT-beta, and lymphoid chemokines (CCL21, CCL19, CXCL13). High endothelial venules (HEVs) developed that expressed GlyCAM-1, HEC-6ST [an enzyme crucial for expression of luminal peripheral node addressin (PNAd)], and PNAd itself. LT-beta(-/-) and LT-alpha(-/-) NALTs had fewer cells than those of wild-type mice, reduced (LT-beta(-/-)) or absent (LT-alpha(-/-)) lymphoid chemokines, and no T- and B-cell compartmentalization. LT-beta(-/-) HEVs expressed only abluminal PNAd and no HEC-6ST or GlyCAM-1. LT-alpha(-/-) HEVs had no PNAd, HEC-6ST, or GlyCAM-1. Because intranasal immunization gives rise to vaginal IgA, immunization of LT-beta(-/-) mice, which retain cervical lymph nodes, might generate such a response. Intranasal immunization with ovalbumin and cholera toxin revealed lower cytokine levels in the LT-alpha(-/-) and LT-beta(-/-) NALTs, and undetectable vaginal IgA. In contrast, splenic cytokines and serum IgG titers, although reduced, were detectable. These data indicate that LT-alpha(3) and LT-alpha(1)beta(2) cooperatively contribute to NALT development and function through regulation of lymphoid chemokines and adhesion molecules; they are the first to implicate LT-alpha(1)beta(2) in GlyCAM-1 regulation in NALT HEV development.
关于细胞因子、趋化因子和血管地址素的作用，鼻相关淋巴组织（NALT）发育的机制尚未完全明确。野生型NALT在出生后即刻继续发育，细胞数量逐渐增加，分化为T细胞区和B细胞区，并表达淋巴毒素（LT）-α、LT-β和淋巴趋化因子（CCL21、CCL19、CXCL13）。高内皮微静脉（HEV）发育形成，其表达GlyCAM-1、HEC-6ST[一种对腔内外周淋巴结地址素（PNAd）表达至关重要的酶]以及PNAd本身。与野生型小鼠相比，LT-β（-/-）和LT-α（-/-）的NALT细胞数量较少，淋巴趋化因子减少（LT-β（-/-））或缺失（LT-α（-/-）），且不存在T细胞和B细胞分区。LT-β（-/-）的HEV仅表达腔外PNAd，不表达HEC-6ST或GlyCAM-1。LT-α（-/-）的HEV不表达PNAd、HEC-6ST或GlyCAM-1。由于鼻内免疫可产生阴道IgA，保留颈部淋巴结的LT-β（-/-）小鼠免疫后可能产生这种反应。用卵清蛋白和霍乱毒素进行鼻内免疫显示，LT-α（-/-）和LT-β（-/-）的NALT中细胞因子水平较低，且未检测到阴道IgA。相比之下，脾脏细胞因子和血清IgG滴度虽有所降低，但仍可检测到。这些数据表明，LT-α3和LT-α1β2通过调节淋巴趋化因子和黏附分子，共同促进NALT的发育和功能；首次表明LT-α1β2在NALT的HEV发育中对GlyCAM-1的调节作用。
