Th2-TRMs Maintain Life-Long Allergic Memory in Experimental Asthma in Mice

Abstract

Allergic asthma is a chronic inflammatory remitting-relapsing disease affecting the airways. Long-lived allergen-specific memory CD4 + T helper 2 (Th2) cells in mice persist in lungs for more than 2 years after the induction of experimental allergic asthma (EAA). To further understand lung Th2 memory cells, we tracked CD4 + T cells in spleen and lungs from healthy mice, through the initiation of acute EAA, recovery (remission), and allergen-induced disease relapse. We identified a lung CD3 + CD4 + cell subset that expresses CD44 hi CD62L − CD69 + ST2 + , produces Th2 cytokines, and mediates allergen-induced disease relapse despite treatment with FTY720 and anti-CD4 antibody. These cells reside in the lung tissue for the lifetime of mice (>665 days) and represent long-lived pathogenic Th2 tissue resident memory cells (T RMs ) that maintain “allergic memory” in lung. We speculate that these data implicate that human Th2-T RMs sentinels in lungs of patients are poised to rapidly respond to inhaled allergen and induce asthma attacks and that therapeutic approaches targeting these cells may provide relief to patients with allergic asthma.

Allergen-Specific Immunotherapy With Liposome Containing CpG-ODN in Murine Model of Asthma Relies on MyD88 Signaling in Dendritic Cells

“…Allergen-specific immunotherapy aims to provide sustained inhibition of the disease symptoms (35). Given that T cell memory is long-lasting in the OVA-induced allergic respiratory model (36) and that allergen-specific immunotherapy usually require many weeks or years of treatment (37,38) we then next investigated whether our short-term (three-dose) treatment provides a long-lasting effect. For this, after the treatment, the mice were rested for 60 days and then challenged twice with i.n.…”

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

“…It has been shown that sustained allergic inflammation in the lower airway may require an abundant presence of readily primed memory T cells in peripheral blood that can respond to allergens [35]. CD4+ memory T cells were shown to be involved in recurrent episodes of inflammation in both murine models of BA and BA patients [36,37]. We hypothesized that memory T cells in BA patients display distinctive phenotypes that can sustain chronic inflammation in the lung; and that the expression of certain chemokine receptors on T cells is associated with disease severity and worsening of symptoms.…”

Legend of the Sentinels: Development of Lung Resident Memory T Cells and Their Roles in Diseases

“…IL-2 up-regulates chemokine receptors such as CCR4 and CXCR3 that improve migration into the lung, as well as programs related to tissue intention ( 64 ). A recently published paper further reports that these T H 2-T RM cells highly express CD44 and ST2, and can reside in lung tissue and maintain their memory towards allergen for the whole life of a mouse ( 65 ). Once re-exposed to allergen, T H 2-T RM cells robustly proliferate near airways, produce type 2 cytokines, enhance eosinophil activation, and promote peribronchial inflammation.…”