Publications & Reports

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'Hehir RE
Department of Immunology, Monash University, Australia.


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.


  • Journal: Journal of Immunology
  • Published: 01/05/2010
  • Volume: 184
  • Issue: 9
  • Pagination: 4708-4716