The Effector T Cell Response to Ryegrass Pollen Is Counterregulated by Simultaneous Induction of Regulatory T Cells

Mittag, D; Scholzen, A; Varese, N; Baxter, L; Paukovics, G; Harrison, LC; Rolland, JM; O&#39;Hehir, RE

Author(s): Mittag, D; Scholzen, A; Varese, N; Baxter, L; Paukovics, G; Harrison, LC; Rolland, JM; O'Hehir, RE;
Details: Publication Year 2010-05-01,Volume 184,Issue #9,Page 4708-4716
Journal Title: JOURNAL OF IMMUNOLOGY
Publication Type: Journal Article
Abstract: Allergy is associated with pathological Th2 responses to otherwise harmless environmental Ags. In contrast, nonallergic individuals mount nonpathological immune responses to allergens, partly attributed to regulatory T cell (Treg) activity. Although thymus-derived natural Tregs have been shown to maintain tolerance to self-Ags and prevent autoimmunity, the generation of Tregs specific to non-self-Ags is less well understood. We investigated the potential for induction of Tregs from PBMCs of ryegrass pollen-allergic or healthy subjects by stimulation in vitro with ryegrass pollen extract in the absence of additional exogenous stimuli. We found that two subsets of proliferating CD4(+) T cells were induced, one expressing intermediate levels of Foxp3 (and IFN-gamma, IL-4, IL-17, or IL-2) and the other expressing high levels of Foxp3 (and no effector cytokines). After enrichment based on CD39 expression, the Foxp3(hi) subset suppressed CD4(+) T cell proliferation and IFN-gamma production. The Foxp3(hi) Treg originated from both conversion of dividing non-Tregs (CD4(+)CD25(-)CD127(hi)) and expansion of natural Tregs (CD4(+)CD25(+)CD127(lo)). Stable functional Tregs expressing high levels of Foxp3 were induced simultaneously with effector T cells by allergen stimulation. Induction of Foxp3(hi) Tregs was reduced in allergic subjects. These results indicate that the cogeneration of Foxp3(hi) Tregs in response to allergen may be a mechanism for controlling allergic reactions in healthy individuals, which is impaired in those with allergies. The Journal of Immunology, 2010, 184: 4708-4716.
Publisher: AMER ASSOC IMMUNOLOGISTS
Keywords: IMMUNE SUPPRESSION; CUTTING EDGE; TREG CELLS; FOXP3; EXPRESSION; ALLERGEN; ACTIVATION; GENERATION; PROLIFERATION; PHENOTYPE
Publisher's Version: https://doi.org/10.4049/jimmunol.0901036
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2010-05-01 12:00:00