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

Summary: Objective. CD4+T cell subtypes are the central orchestrators of airway inflammation in bronchialasthma (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 acquireantigen 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 andCCR4+ 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 andnon-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 up regulation 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. Conclusions. 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.