Staphylococcal enterotoxin A–activated regulatory T cells promote allergen-speciﬁc TH2 response to intratracheal allergen inoculation
Background: TH2responsesareimplicatedinasthmapathobiology. Epidemiologic studies have found a positive association between asthma and exposure to staphylococcal enterotoxins. Objective: We used a mouse model of asthma to determine whether staphylococcal enterotoxins promote TH2 differentiation of allergen-speciﬁc CD4 conventional T (Tcon) cells and asthma by activating allergen-nonspeciﬁc regulatory T (Treg) cells to create a TH2-polarizing cytokine milieu. Methods: Ovalbumin (OVA)–speciﬁc, staphylococcal enterotoxin A (SEA)–nonreactive naive CD4 Tcon cells were cocultured with SEA-reactive allergen-nonspeciﬁc Treg or CD4 Tcon cells in the presence of OVA and SEA. The OVA-speciﬁc CD4 T cells were then analyzed for IL-13 and IFN-g expression. SEA-activated Treg cells were analyzed for the expression of the TH2-polarizing cytokine IL-4 and the T-cell activation markers CD69 and CD62L. For asthma induction, mice were intratracheally sensitized with OVA or cat dander extract (CDE) alone or together with SEA and then challenged with OVA or CDE. Mice were also subject to transient Treg cell depletion before sensitization with OVA plus SEA. Asthma features and TH2 differentiation in these mice were analyzed. Results: SEA-activated Treg cells induced IL-13 but suppressed IFN-g expression in OVA-speciﬁc CD4 Tcon cells. SEAactivated Treg cells expressed IL-4, upregulated CD69, and downregulated CD62L. Sensitization with OVA plus SEA but not OVA alone induced asthma, and SEA exacerbated asthma induced by CDE. Depletion of Treg cells abolished these effects of SEA and IL-13 expression in OVA-speciﬁc T cells. Conclusion: SEA promoted TH2 responses of allergen-speciﬁc T cells and asthma pathogenesis by activating Treg cells.
Zeng WP, McFarland MM, Zhou B, Holtfreter S, Flesher S, Cheung A, Mallick A. Staphylococcal enterotoxin A–activated regulatory T cells promote allergen-specific TH2 response to intratracheal allergen inoculation. Journal of Allergy and Clinical Immunology. 2017;139(2):508-18.