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

• Published in: The Journal of experimental medicine Vol. 202; no. 11; pp. 1549 - 1561
• Main Authors: Lewkowich, Ian P, Herman, Nancy S, Schleifer, Kathleen W, Dance, Matthew P, Chen, Brian L, Dienger, Krista M, Sproles, Alyssa A, Shah, Jaimin S, Koehl, Joerg, Belkaid, Yasmine, Wills-Karp, Marsha
• Format: Journal Article
• Language: English
• Published: 05-12-2005
• Subjects: Dermatophagoides pteronyssinus
• ISSN: 0022-1007; 1892-1007

The role of natural CD4 super(+)CD25 super(+) 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 super(+)CD25 super(+) T reg cell suppression of DC activation and that the absence of this regulatory pathway contributes to susceptibility.