We appreciate that G. Lezmi and M. Leite-de-Moraes called attention to our recent publication (1) on mucosal-associated invariant T (MAIT) cells and childhood asthma. We are pleased that their interesting, recent work also finds a link between MAIT cells and this disease. This is logical, considering that MAIT cells are relatively abundant, they secrete effector cytokines, and they can home to the lung. Lezmi et al. (2) found increased IL-17A production by activated MAIT cells from the blood of school children with severe asthma, but in their comment they show that IFN-γ production by MAIT cells was not correlated with disease protection. By contrast, whereas our data indicated that MAIT cell number correlated with protection from disease, the ability of activated MAIT cells from the blood to produce IFN-γ (1) or to produce IL-17A (Fig. 1) was not associated with the development of asthma. The results are not contradictory and the difference is not surprising, considering the very different study designs. Lezmi et al. (2) analyzed 19 French children, average age ∼11 y, all with asthma. They compared those with exacerbations to those that did not have them. By contrast, our report analyzed the blood of 1-y-old children who are predominantly African American and living in high poverty, urban neighborhoods in the United States, and we compared those who developed asthma by age 7 y to those who did not. Thus, there are differences in the age of the subjects, their ethnic backgrounds, and their environment and, importantly, we analyzed the children long before they showed any signs of symptoms. A synthesis of these results is that more MAIT cells in the blood early in life is correlated with protection from asthma, whereas in severe cases, an increased capacity of blood MAIT cells to produce IL-17A is correlated with more severe disease. Further research will be required, however, to determine if these findings can be replicated in other cohorts, and if the number and/or function of MAIT cells is only correlative or truly contributing to the cause or prevention of asthma.
IL-17 production by activated MAIT cells in 1-y-old children does not correlate with asthma at age 7 y. Shown is the frequency of IL-17A+ MAIT cells in 1-y-old children that did (Pos, n = 13) or did not (Neg, n = 71) develop asthma at age 7 y. PBMCs were stimulated with PMA and ionomycin for 4 h in the presence of GolgiPlug and GolgiStop. The p values were calculated using a Student t test.
Footnotes
This work was supported by the National Institute of Allergy and Infectious Diseases/National Institutes of Health (NIH) under Contracts NO1-AI-25496, NO1-AI-25482, HHSN272200900052C, HHSN2722010000521, 1UM1AI114271-01, and UM2AI117870. Additional support was provided by the National Center for Research Resources/NIH under Grants AI71922, 5T32AI007007, RR00052, M01RR00533, 1UL1RR025771, M01RR00071, 1UL1RR024156, 5UL1RR024992-02, and UM1 AI114271.
Abbreviations used in this article:
- MAIT
- mucosal-associated invariant T.
- Copyright © 2018 by The American Association of Immunologists, Inc.