Clonal Expansion of Allergen-specific CD4⁺ T Cell in the Lung in the Absence of Lymph Nodes

ABSTRACT

The expansion of allergen-specific CD4⁺ T cells is a critical step in inducing airway inflammation during allergic asthma. Such clonal expansion of T cells is initiated through the interaction between allergen-bearing dendritic cells and allergen-specific naïve T cells in the draining lymph nodes. Whether such T cell clonal expansion also occurs in the lung, the primary organ encountering inhaled allergens, remains unclear. Compared with wild-type mice, we found similar frequencies of CD4⁺ T cells in the lung of lymph node-deficient Rorgt(gfp/gfp) mice after repeated exposure to inhaled allergens. In addition, we observed an evident population of CD4⁺ T cells that underwent clonal expansion in the lung of allergen-challenged mice treated with an S1P antagonist FTY720 in an in vivo proliferation study with CFSE-labeled OT-II T cells. Moreover, the expansion of allergen-specific CD4⁺ T cells was significantly enhanced in the lungs of Rorgt(gfp/gfp) mice in comparison to that of wild-type mice. These results together demonstrate that the clonal expansion of allergen-specific CD4⁺ T cells occurs in the absence of the lymph nodes, indicating that the lung can act as a primary site of the clonal expansion of CD4⁺ T cells in response to inhaled allergens.