Clin Transl Allergy
National Center for Research Resources, and National Center for Advancing Translational Sciences, National Institutes of Health, Grant/ Award Numbers: NCATS/NIH UL1TR001079, NCATS/NIH UL1TR001422, NCATS/NIH UL1TR001876, NIAID/NIH U19AI135731, NIH/CTSA 5UL1TR001425‐03; National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, Grant/Award Numbers: 1UM1AI114271‐01, 5UM1AI114271‐03, UM2AI117870
T cell; allergens; asthma; clinical immunology; cockroach.
Background: Characterization of allergic responses to cockroach (CR), a common aeroallergen associated with asthma, has focused mainly on IgE reactivity, but little is known about T cell responses, particularly in children. We conducted a functional evaluation of CR allergen-specific T cell reactivity in a cohort of CR allergic children with asthma.
Methods: Peripheral blood mononuclear cells (PBMCs) were obtained from 71 children, with mild-to-moderate asthma who were enrolled in a CR immunotherapy (IT) clinical trial, prior to treatment initiation. PBMC were stimulated with peptide pools derived from 11 CR allergens, and CD4+ T cell responses assessed by intracellular cytokine staining.
Results: Highly heterogeneous responses in T cell reactivity were observed among participants, both in terms of the magnitude of cytokine response and allergen immunodominance. Reactivity against Bla g 9 and Bla g 5 was most frequent. The phenotype of the T cell response was dominated by IL-4 production and a Th2 polarized profile in 54.9% of participants, but IFNγ production and Th1 polarization was observed in 25.3% of the participants. The numbers of regulatory CD4+ T cells were also highly variable and the magnitude of effector responses and Th2 polarization were positively correlated with serum IgE levels specific to a clinical CR extract.
Conclusions: Our results demonstrate that in children with mild-to-moderate asthma, CR-specific T cell responses display a wide range of magnitude, allergen dominance, and polarization. These results will enable examination of whether any of the variables measured are affected by IT and/or are predictive of clinical outcomes.
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da Silva Antunes, R., Sutherland, A., Frazier, A., Schulten, V., Pomés, A., Glesner, J., Calatroni, A., Altman, M., Wood, R., O'Connor, G., Pongracic, J., Khurana Hershey, G., Kercsmar, C., Gruchalla, R., Gill, M., Liu, A., Zoratti, E., Kattan, M., Busse, P., Bacharier, L., Teach, S. J., Wheatley, L., Togias, A., Busse, W., Jackson, D., & Sette, A. (2021). Heterogeneity of magnitude, allergen immunodominance, and cytokine polarization of cockroach allergen-specific T cell responses in allergic sensitized children.. Clin Transl Allergy, 11 (8). http://dx.doi.org/10.1002/clt2.12073