Abstract
Tertiary lymphoid organs (TLOs) are aggregates of B and T cells formed in response to chronic immune responses. TLOs are the result of lymphoid neogenesis and are formed via production of lymphoid-organizing chemokines (CXCL13, CCL19 and CCL21), in response to signaling from lymphotoxin α (LTα) via TNFR1, TNFR2 and LTR. Stromal cells and antigen presenting cells (APCs), i.e. dendritic cells (DCs), secrete lymphoid chemokines, which attract B cells, T cells and DCs via CCR7 (receptor for CCL19/21) and CXCR5 (receptor for CXCL13). Lymphoid follicles are frequently found in the peripheral lungs of patients with Chronic Obstructive Pulmonary Disease (COPD). Whether they are the result of lymphoid neogenesis remains elusive. Here, we have identified 18 patients with COPD and lymphoid follicles and used immunohistochemistry to analyze the expression of LTa and lymphoid chemokines. Flow cytometry was applied to study expression of their receptors. LTα is abundantly expressed by alveolar macrophages and lung stromal cells and CXCL13 is strongly expressed inside the follicles. HLA-DR+ve cells (APCs), but not CD45-ve stromal cells, strongly express TNFR1 (43% of APCs), TNFR2 (47%) and LTR (38%). CXCR5 is expressed by B cells (96% of B cells), DCs (74% of DCs) and T cells (24% of T cells). CCL19, CCL21 and CCR7 are rarely expressed. In conclusion, molecular mechanisms underlying TLO formation might be involved in lymphoid follicle formation in COPD as follows: stromal cells and macrophages secrete LTa, which induces CXCL13 production by lung APCs, driving the accumulation of CXCR5 bearing B cells, T cells and DCs to sites of TLO. Funded by the Hellenic Thoracic Society.
- © 2011 ERS