Elevated pulmonary levels of CXCL12, CXCL13 and cholesterol metabolites, produced during COPD, attract cDC2 and CD4+ T-cells to the site of TLO formation. Upon encounter, cDC2 drive IL-21+ Tfh-like cell polarization via the OX40L-OX40 axis and the secretion of cytokines like IL-6, IL-1β and TGF-β. The chronicity of this self-amplifying loop results in the formation of well-established TLOs during late-stage COPD in which Tfh-like cell clonality and proliferation is further sustained by cDC2.