Allergen-specific regulatory T cells form lung resident memory capable of suppressing Th2 recall responses to allergen 4564

Abstract Description Intranasal house dust mite (HDM) exposure elicits allergen-peptide (p):MHCII-specific Th2 and Tregs in the airways of mice. The balance between opposing pro- and anti-inflammatory functions of these cell populations may influence the outcome of airway re-exposure to HDM. However, the number of cells specific for known HDM derived epitopes in wild type B6 mice is low, making longitudinal studies of these cell populations difficult. We used adoptive transfer of a physiologically relevant number of CD4+ T cells from a fixed TCR beta chain transgenic (1-DERβ) mouse and corresponding HDM p:MHCII tetramer to simultaneously interrogate the trafficking, memory cell formation, and functional properties of HDM-specific Th2 and Treg cells. Naïve 1-DERβ CD4+ T cells generated similar frequencies of Th2 and Treg fates as endogenous HDM-specific cells. Parabiosis experiments demonstrated HDM-specific Tregs form stable tissue-resident memory (Trm) cells in the lungs, similar to their previously described Th2 counterparts. Single cell RNA sequencing of these cell populations and revealed shared expression of Trm genes, including the chemokine receptors CXCR6 and CCR8. Depletion of Tregs in the memory phase led to increased Th2 responses in the lung. Thus, our findings are consistent with a model where allergen-specific Tregs are positioned in a unique niche in the allergic lung juxtaposed to Th2 cells that enables potent suppression of allergic inflammation following allergen rechallenge. Funding Sources Supported by NIH AI171176 (to R.W.N.) and R01AI168131 (to A.D.L.) Topic Categories Immediate Hypersensitivity, Asthma, and Allergic Responses (HYP)