Immune signature of CCR7+ central memory T cells associates with disease severity and Immunoglobulin E in bronchial asthma

Abstract

Objectives: CD4+T cell subtypes are the central orchestrators of airway inflammation in bronchial asthma (BA); however, the mechanisms that regulate their accumulation in asthmatic airways are still a challenging subject. In addition, neutrophils play a significant role in the development of airway remodeling and their presence may influence clinical presentation of BA being linked to the development of severe BA. Neutrophils have also been found to acquire antigen presenting functions, enabling them to directly activate T cells. The study aimed to evaluate the possible association of chemokine receptor 7 (CCR7)+ memory CD4+ T cells and CCR4+ effector T cells with disease severity and immunoglobulin E (IgE) production as well as to explore the relationship between these cells and neutrophil function in both allergic and non-allergic asthmatic patients. Methods: Flow cytometry was used to determine the expression of different T cell subset phenotypes (CCR7 memory CD4+ and CCR4+ T cells using anti-human CD3, CD4, CD45RO, CCR4 and CCR7 monoclonal antibodies) utilizing peripheral blood mononuclear cells (PBMCs) isolated from 78 allergic asthmatic patients, 41 non-allergic asthmatic patients, and 40 healthy individuals. Moreover, neutrophils' phagocytic activity was assessed by ingestion of candida particles. Results: We demonstrated increased percentages of CCR7+ memory CD4+ T cells and CCR4+ CD4+ T cells in patients compared to control, where this upregulation was significantly higher in allergic than non-allergic asthmatic patients. Additionally, these cells were negatively correlated with improved pulmonary tests and significantly associated with disease severity scores and IgE levels. The neutrophil phagocytic activity was markedly increased in patients compared to control, showing a significant positive correlation with disease severity. Conclusion: These findings suggest that increased CCR4+ CD4+ T cells and CCR7+ memory CD4+ T cells (Tcm) may be associated with BA severity, especially in allergic BA patients and can potentially contribute to the rational design of new therapeutic approaches for asthma in the future.

Lipopolysaccharide-Activated Bone Marrow-Derived Dendritic Cells Suppress Allergic Airway Inflammation by Ameliorating the Immune Microenvironment

“…There was no difference in the cell numbers of T CM and T EM among the groups. It has been reported that the immune characteristics of CCR7 + T CM were significantly correlated with asthma severity and IgE levels, and the proportion of CCR7 + T CM in peripheral blood mononuclear cells (PBMC) in patients with allergic asthma was significantly higher than that in patients without allergic asthma (22). However, the airway immune microenvironment of asthma is complex and ample experimental evidence supports that T CM and T EM cells can be converted to the other cell type in many conditions (21,23), hence, the exact mutual proportion of T CM and T EM need to be further investigated in the future.…”

“…Allergen-specific Th2 memory cells have been viewed as fundamental for the development of allergic asthma in both human and animal models ( 22 ), and DC regulate the generation of memory T cells at each stage via the interplay between these cells ( 38 ). T CM has the characteristics of self-renewal ability and long-term memory, which can proliferate after antigen restimulation; while the proliferation ability of T EM is lower than T CM , whose function is similar to effector T cell ( 24 ).…”

“…It is widely believed that Th1/Th2 ratio imbalances may lead to the pathogenesis of allergic asthma, in which memory T cells play a crucial role in the capacity of initiating Th2 response under repeated allergen challenges (21,22). Memory T cells can be divided into two distinct subsets, central memory T cells (T CM ) and effector memory T cells (T EM ), according to their homing characteristics and effector functions (23,24).…”

Anti-inflammatory Mechanism of Astragaloside IV in the Recurrence of Asthma: Critical Role of Memory T Cells and OX40/OX40L Signaling Pathway

“…of these control mechanisms is the ability to inhibit the differentiation of T CM . Yet, a recent report showed that in severe asthma patients, the percentage of CCR7 high memory T cells in the blood was signi cantly lower than in the control group; thus, the distribution between lung, blood and peripheral lymphatic organs may be disordered in severe asthma [29]. Previous research has described that AST had an anti-in ammatory effect and could prevent the recurrence of asthma [30].…”

“…Central memory T cells enter into secondary lymphoid organs, proliferate, and produce a higher percentage of effector memory phenotype cells, which are to the acute in ammation in lung tissues [27]. A recent report also revealed that increased CCR7 high central memory T cells were associated with asthma severity [28]. of these control mechanisms is the ability to inhibit the differentiation of T CM .…”