Accumulation Of Allergen-Specific Cd4+T Cells In The Airways After Segmental Allergen Challenge Is Associated With Reduced Expression Of T2 Chemoattractant Receptors On Allergen-Specific Cd4+T Cells In Blood

CD4+ Th2 cells are recruited to the airways following inhaled and segmental allergen challenge. Concentrations of Th2-cell-associated (T2) cytokines (e.g. IL-5, IL-9) and T2 chemoattractants (e.g. CCL26, PGD2) are increased in the bronchoalveolar lavage (BAL) following challenge, implying recruitment of Th2 cells to the lung via these mediators. We hypothesized that accumulation of allergen-specific CD4+ T cells in the BAL is associated with loss of these cells from peripheral blood. Segmental allergen challenge was performed in 38 cat allergic asthmatics. BAL was harvested from saline- and allergen-challenged lobes after 24hrs. Blood was collected at baseline (BL), 6 and 24hrs. Fel d 1-specific CD4+ T cells were identified and enumerated using Fel d 1 MHC class II tetramers. Phenotyping for chemoattractant receptors was performed by flow cytometry. Segmental allergen challenge was associated with airway eosinophilia and reduced methacholine PC20. The frequency of tetramer+ T cells in the allergen- vs. saline-challenged segment was significantly increased (mean [±SD] Tet+ cells/106 T cells: 3542 [±5942] saline vs. 9200 [±8879] allergen, p=0.03). Unexpectedly, the frequency of tetramer+ T cells increased over time in the blood (BL-6hrs: p=0.04; BL-24hrs: p=0.005). The frequency of CCR3+, CCR5+ and CRTh2+ tetramer+ T cells decreased significantly over time (BL-24hrs), whereas the frequency of tetramer+ T cells expressing CCR4, CCR6, CCR7, CCR8, CXCR3, and CXCR4 did not. Increased frequency of allergen-specific T cells in the BAL and decreased frequency of cells expressing T2 chemoattractant receptors in the blood following allergen challenge implies chemoattractant-dependent recruitment from the blood to the airways.