Allergy and asthma in inner-city children: possible roles of MAIT cells and variation in the home environment

Abstract

Abstract Humans have two populations of innate-like T lymphocytes with an invariant T cell antigen receptor (TCR) a chain: invariant natural killer T (iNKT) cells and mucosal associated invariant T (MAIT) cells. iNKT cell involvement in human asthma has been suggested, but is controversial, while there has been little analysis of MAIT cells. Using peripheral blood cells from the urban environment and childhood asthma (URECA) birth cohort study, we carried out a comprehensive investigation to determine if iNKT cell frequency or MAIT cell frequency early in life is correlated with the cytokine polarization of mainstream CD4+T cells and/or the development of asthma by age seven. We also determined if iNKT cell antigenic activity in house dust samples was associated with environmental endotoxin or clinical outcomes including aeroallergen sensitization and recurrent wheeze at 3 and asthma at age 7. We also analyzed the correlation between cytokines released by activated iNKT and MAIT cells and various clinical outcomes. Our results shows that the frequency of MAIT cells was associated with increased production of IFNg by activated CD4+ T cells from children that did not go on to develop asthma. Moreover, an increased MAIT cell frequency early in life was associated with a decreased risk of asthma by age seven. In contrast, iNKT cell frequency early in life was not correlated with the development of asthma or allergic sensitization. iNKT cell antigen content in house dust varied greatly, and increased antigen was associated not only with endotoxin levels in the surroundings but also with protection from asthma. Together, these data suggest that MAIT cell frequency and iNKT cell antigen content at one year correlates with protection from asthma development.