IL-7 plays a critical role for the homeostasis of allergen-specific memory CD4 T cells in the lung and airways

Seung-Min Yeon,Sun-Uk Kim,Susan M Kaech,Sang Hoon Kim,Anmol Chandele,Soon Hong Yuk,Curtis J Perry,Yong Woo Jung,Youngjoo Byun,Lea Halim

doi:10.1038/s41598-017-11492-7

Abstract

Memory T cells respond rapidly to repeated antigen exposure and can maintain their population for extended periods through self-renewal. These characteristics of memory T cells have mainly been studied during viral infections, whereas their existence and functions in allergic diseases have been studied incompletely. Since allergic patients can suffer repeated relapses caused by intermittent allergen exposure, we hypothesized that allergen- specific memory Th2 cells are present and the factors necessary for the maintenance of these cells are provided by the lung and airways. Using a murine model of airway inflammation, we found that allergen-specific CD4 T cells survived longer than 70 days in the lung and airways in an IL-7 dependent fashion. These T cells showing homeostatic proliferation were largely found in the mediastinal lymph node (mLN), rather than the airways; however, cells residing in the lung and airways developed recall responses successfully. We also found that CD4 T cells exhibited differential phenotypes in the mLN and in the lung. Altogether, we believe that allergen-specific memory T cells reside and function in the lung and airways, while their numbers are replenished through homeostatic turnover in the mLNs. Furthermore, we determined that IL-7 signaling is important for the homeostasis of these cells.

Highlights

Allergic asthma is a chronic allergic disease characterized by eosinophilic airway inflammation and hyperreactivity[1,2,3,4]
On days 7, 30, and 70 post challenge these mice were sacrificed to measure the number of OVA-specific CD4 T cells in the spleen, mediastinal lymph node, lung, and bronchoalveolar lavage (BAL) fluid
We found that the number of these cells peaked on day 7 and declined on day 30 and 70 in these organs (Fig. 1b). We examined if these long-lived allergen-specific CD4 T cells can induce eosinophilic inflammation following rechallenge

Summary

Introduction

Allergic asthma is a chronic allergic disease characterized by eosinophilic airway inflammation and hyperreactivity[1,2,3,4]. We observed that the number of OVA-specific CD4 T cells increased in response to recall, and the mice developed eosinophilic inflammation (Supplementary Fig. 1b and c). We suggest that allergen-specific CD4 T cells in the process of memory T cell maturation proliferate mainly in the mLN, while these cells are continuously recruited into the lung and airways to maintain their numbers in these organs.

Results

Conclusion