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 (T_EM) and central memory (T_CM) 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 T_CM 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 T_CM cells in inflamed lungs compared to healthy controls. Interestingly, adoptive transfer techniques confirmed substantial infiltration of T_CM cells to lung tissues during allergic airway inflammation. Expression levels of T_CM homing receptors, CD34 and GlyCAM-1, were also significantly upregulated in the lung tissues of OVA-sensitized mice, which may facilitate the increased T_CM infiltration into inflamed lungs. Moreover, a substantial increase in the relative expression of T_CM profile-associated genes (EOMES, BCL-6, ID3, TCF-7, BCL-2, BIM, and BMI-1) was noted for T_EM cells during lung inflammation, suggesting a shift for T_EM into the T_CM state. To our knowledge, this is the first study to report an increased infiltration of T_CM cells into inflamed lung tissues and to suggest differentiation of T_EM to T_CM cells in these tissues. Therapeutic interference at T_CM infiltration or differentiations could constitute an alternative treatment approach for lung inflammation.