Role of CXC Chemokine Ligand 13, CC Chemokine Ligand (CCL) 19, and CCL21 in the Organization and Function of Nasal-Associated Lymphoid Tissue

摘要

Nasal-associated lymphoid tissue (NALT) orchestrates immune responses to Ags in the upper respiratory tract. Unlike other lymphoid organs, NALT develops independently of lymphotoxin-α (LTα). However, the structure and function of NALT are impaired in Lt α?/? mice, suggesting a link between LTα and chemokine expression. In this study we show that the expression of CXCL13, CCL19, CCL21, and CCL20 is impaired in the NALT of Lt α?/? mice. We also show that the NALT of Cxcl13 ?/? and plt/plt mice exhibits some, but not all, of the structural and functional defects observed in the NALT of Lt α?/? mice. Like the NALT of Lt α?/? mice, the NALT in Cxcl13 ?/? mice lacks follicular dendritic cells, BP3+ stromal cells, and ERTR7+ lymphoreticular cells. However, unlike the NALT of Lt α?/? mice, the NALT of Cxcl13 ?/? mice has peripheral node addressin+ high endothelial venules (HEVs). In contrast, the NALT of plt/plt mice is nearly normal, with follicular dendritic cells, BP3+ stromal cells, ERTR7+ lymphoreticular cells, and peripheral node addressin+ HEVs. Functionally, germinal center formation and switching to IgA are defective in the NALT of Lt α?/? and Cxcl13 ?/? mice. In contrast, CD8 T cell responses to influenza are impaired in Lt α?/? mice and plt/plt mice. Finally, the B and T cell defects in the NALT of Lt α?/? mice lead to delayed clearance of influenza from the nasal mucosa. Thus, the B and T cell defects in the NALT of Lt α?/? mice can be attributed to the impaired expression of CXCL13 and CCL19/CCL21, respectively, whereas impaired HEV development is directly due to the loss of LTα.