Chronic Allergen Stimulation Yields T cell Dysfunction in Obese Asthmatics
Monday, March 5, 2018: 2:30 PM
S220EF (Convention Center)
Sarah E. Henrickson, MD/PhD, , , , , , , , ,
RATIONALE: The connections among atopy, asthma, obesity and immune function remain poorly understood, particularly in pediatric patients. Obese asthmatics have a phenotype of difficult to control disease complicated by severe viral URI triggered exacerbations. The control of viral infections requires CD8 T cell responses, however the potential role of CD8 T cell dysfunction in obese asthma has not been well defined.

METHODS: Prospective study of pediatric asthma and obesity with four groups of patients (6-18 years): obese asthmatics (OA), non-obese asthmatics (A), obese non-asthmatics (O) and non-obese and non-asthmatics (HC). Asthmatics were atopic patients recruited from our Allergy clinic, with deep clinical characterization including sensitization and spirometry. Clinical studies included immune function, metabolic and inflammatory markers. Research studies included water-soluble and lipid-soluble metabolomics, high dimensional cytometry and serum cytokines.

RESULTS: Pediatric atopic obese asthmatics demonstrated immune dysfunction with increased type 2 immune deviation (including more CRTH2+ CD4 T cells and IL-13 secretion) and CD8 T cell exhaustion (concordant expression of multiple inhibitory receptors on CD8 T cells, including PD-1 and Eomes), in the context of altered cytokine and metabolic profiles with evidence of direct immunometabolic mechanisms.

CONCLUSIONS: In the complex OA phenotype we have demonstrated two mechanisms of T cell dysfunction that may partially explain their impaired ability to contain viral URIs: increased CD8 T cell exhaustion and type 2 immune deviation. In atopic OA there is chronic allergen stimulation that may provide the antigen that leads to the underlying immunometabolic tuning. We are currently pursuing these mechanisms in mouse models of pediatric OA.