Enhanced Infiltration of Central Memory T Cells to the Lung Tissue during Allergic Lung Inflammation

Abstract

Memory T cells play a central role in regulating inflammatory responses during asthma. However, tissue distribution of effector memory (TEM) and central memory (TCM) T-cell subtypes, their differentiation, and their contribution to the persistence of lung tissue inflammation during asthma are not well understood. Interestingly, an increase in survival and persistence of memory T cells was reported in asthmatic lungs, which may suggest a shift toward the more persistent TCM phenotype. In this report, we investigated the differential distribution of memory T-cell subtypes during allergic lung inflammation and the mechanism regulating that. Using an OVA-sensitized asthma mouse model, we observed a significant increase in the frequency of TCM cells in inflamed lungs compared to healthy controls. Interestingly, adoptive transfer techniques confirmed substantial infiltration of TCM cells to lung tissues during allergic airway inflammation. Expression levels of TCM homing receptors, CD34 and GlyCAM-1, were also significantly upregulated in the lung tissues of OVA-sensitized mice, which may facilitate the increased TCM infiltration into inflamed lungs. Moreover, a substantial increase in the relative expression of TCM profile-associated genes (EOMES, BCL-6, ID3, TCF-7, BCL-2, BIM, and BMI-1) was noted for TEM cells during lung inflammation, suggesting a shift for TEM into the TCM state. To our knowledge, this is the first study to report an increased infiltration of TCM cells into inflamed lung tissues and to suggest differentiation of TEM to TCM cells in these tissues. Therapeutic interference at TCM infiltration or differentiations could constitute an alternative treatment approach for lung inflammation.

Keywords: Asthma; Central memory T cells; Cytokines; Effector memory T cells; Inflammation; Memory T cells.