CD4+CD25+ T cells protect against experimentally induced asthma and alter pulmonary dendritic cell phenotype and function

Abstract

The role of natural CD4+CD25+ regulatory T (T reg) cells in the control of allergic asthma remains poorly understood. We explore the impact of T reg cell depletion on the allergic response in mice susceptible (A/J) or comparatively resistant (C3H) to the development of allergen-induced airway hyperresponsiveness (AHR). In C3H mice, anti-CD25–mediated T reg cell depletion before house dust mite treatment increased several features of the allergic diathesis (AHR, eosinophilia, and IgE), which was concomitant with elevated T helper type 2 (Th2) cytokine production. In similarly T reg cell–depleted A/J mice, we observed a moderate increase in airway eosinophilia but no effects on AHR, IgE levels, or Th2 cytokine synthesis. As our experiments suggested that T reg cell depletion in C3H mice before sensitization was sufficient to enhance the allergic phenotype, we characterized dendritic cells (DCs) in T reg cell–depleted C3H mice. T reg cell–depleted mice had increased numbers of pulmonary myeloid DCs with elevated expression of major histocompatibility complex class II, CD80, and CD86. Moreover, DCs from T reg cell–depleted mice demonstrated an increased capacity to stimulate T cell proliferation and Th2 cytokine production, which was concomitant with reduced IL-12 expression. These data suggest that resistance to allergen-driven AHR is mediated in part by CD4+CD25+ T reg cell suppression of DC activation and that the absence of this regulatory pathway contributes to susceptibility.

Targeting of CD25 and Glucocorticoid-Induced TNF Receptor Family-Related Gene-Expressing T Cells Differentially Modulates Asthma Risk in Offspring of Asthmatic and Normal Mother Mice

“…3A and data not shown). As previously reported (14,24,25), PC61 mAb depleted CD25 high Treg with little effect on other T cell subsets, including CD25 dim T cells (Fig. 3B).…”

“…Two types of in vivo treatments were performed in 4-day-old naive pups, either aimed to deplete CD25 high T cells by means of PC61 mAb (14,24,25), or to abrogate Treg function by means of DTA-1 mAb agonist of the costimulatory molecule GITR (26,27). Spleen cells were collected, counted, and analyzed by flow cytometry 3 days later.…”

Ex Vivo Rapamycin Generates Apoptosis-Resistant Donor Th2 Cells That Persist In Vivo and Prevent Hemopoietic Stem Cell Graft Rejection

“…Furthermore, the marked in vivo type II cytokine polarization (increased IL-4, IL-5, and IL-10) we observed is not consistent with a strong Treg cell response, because Tregs have been shown to inhibit Th2-type immunity in vivo (61,62). Nonetheless, it is possible that Th2.R cells may be analogous to a Treg cell population that does not express Foxp3, such as the Tr1 population (63).…”

Thioredoxin suppresses airway inflammation independently of systemic Th1/Th2 immune modulation

“…Foxp3 1 Treg cells suppress allergic airway inflammation by inhibiting Th2 cell differentiation in draining LN [38,39]. We recently identified an important role for local Foxp3 1 Treg cells in the lung in the suppression of recruitment and activation of Th2 cells in a model of airway inflammation [40].…”