Lymphotoxin and organogenesis of nasal associated lymphoid tissue

LTα₃ and the LTαβ complex play important roles in lymphoid organogenesis and inflammation. The chemokines and endothelial adhesion molecules were detected by in situ hybridization and immunostaining on the NALTs of 0–21 days of newborn C57BL/6 and adult C57BL/6, LTα−/− and LTβ−/− mice. From day 4 to day 21 of newborn C57BL/6 mice, the number of cells in nasal associated lymphoid tissue (HALT) of newborn was increased with enhanced chemokine (CCL21, CCL19, CXCL 13) mRNA expression. By day 21, the compartmentalization of chemokine was detected with clearly distinct T and B cell areas and the expression of peripheral node addressin (PNAd) also changed from undetectable to abluminal and then luminal correlating with a high endothelial venule (HEV) sulfortransferase (HEVST). LT contributes to NALT development. The expression of lymphoid chemokines were reduced in LTβ−/− or absent in LTα−/− mice. LTβ−/− mice retained only abluminal PNAd expression and no HEVST. LTα−/− mice had no PNAd or HEVST. LTβ−/− and LTα−/− mice retained the NALT structure with reduced numbers of cells and loss of T and B cell compartmentalization. These data indicate that LTα ₃ and LTαβ contribute to NALT development through regulation of lymphoid chemokines and PNAd.