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

Ian P. Lewkowich, Nancy S. Herman, Kathleen W. Schleifer, Matthew P. Dance, Brian L. Chen, Krista M. Dienger, Alyssa A. Sproles, Jaimin S. Shah, Jörg Köhl, Yasmine Belkaid, Marsha Wills-Karp

Research output: Contribution to journalArticle

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. JEM

Original languageEnglish (US)
Pages (from-to)1549-1561
Number of pages13
JournalJournal of Experimental Medicine
Volume202
Issue number11
DOIs
StatePublished - Dec 5 2005
Externally publishedYes

Fingerprint

Dendritic Cells
Asthma
T-Lymphocytes
Phenotype
Lung
Inbred C3H Mouse
Eosinophilia
Cytokines
Allergens
Immunoglobulin E
Pyroglyphidae
Disease Susceptibility
Myeloid Cells
Interleukin-12
Major Histocompatibility Complex
Cell Proliferation

ASJC Scopus subject areas

  • Immunology

Cite this

CD4+CD25+ T cells protect against experimentally induced asthma and alter pulmonary dendritic cell phenotype and function. / Lewkowich, Ian P.; Herman, Nancy S.; Schleifer, Kathleen W.; Dance, Matthew P.; Chen, Brian L.; Dienger, Krista M.; Sproles, Alyssa A.; Shah, Jaimin S.; Köhl, Jörg; Belkaid, Yasmine; Wills-Karp, Marsha.

In: Journal of Experimental Medicine, Vol. 202, No. 11, 05.12.2005, p. 1549-1561.

Research output: Contribution to journalArticle

Lewkowich, IP, Herman, NS, Schleifer, KW, Dance, MP, Chen, BL, Dienger, KM, Sproles, AA, Shah, JS, Köhl, J, Belkaid, Y & Wills-Karp, M 2005, 'CD4+CD25+ T cells protect against experimentally induced asthma and alter pulmonary dendritic cell phenotype and function', Journal of Experimental Medicine, vol. 202, no. 11, pp. 1549-1561. https://doi.org/10.1084/jem.20051506
Lewkowich, Ian P. ; Herman, Nancy S. ; Schleifer, Kathleen W. ; Dance, Matthew P. ; Chen, Brian L. ; Dienger, Krista M. ; Sproles, Alyssa A. ; Shah, Jaimin S. ; Köhl, Jörg ; Belkaid, Yasmine ; Wills-Karp, Marsha. / CD4+CD25+ T cells protect against experimentally induced asthma and alter pulmonary dendritic cell phenotype and function. In: Journal of Experimental Medicine. 2005 ; Vol. 202, No. 11. pp. 1549-1561.
@article{0f84a9a7508e46daa576424eea8dc6c6,
title = "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. JEM",
author = "Lewkowich, {Ian P.} and Herman, {Nancy S.} and Schleifer, {Kathleen W.} and Dance, {Matthew P.} and Chen, {Brian L.} and Dienger, {Krista M.} and Sproles, {Alyssa A.} and Shah, {Jaimin S.} and J{\"o}rg K{\"o}hl and Yasmine Belkaid and Marsha Wills-Karp",
year = "2005",
month = "12",
day = "5",
doi = "10.1084/jem.20051506",
language = "English (US)",
volume = "202",
pages = "1549--1561",
journal = "Journal of Experimental Medicine",
issn = "0022-1007",
publisher = "Rockefeller University Press",
number = "11",

}

TY - JOUR

T1 - CD4+CD25+ T cells protect against experimentally induced asthma and alter pulmonary dendritic cell phenotype and function

AU - Lewkowich, Ian P.

AU - Herman, Nancy S.

AU - Schleifer, Kathleen W.

AU - Dance, Matthew P.

AU - Chen, Brian L.

AU - Dienger, Krista M.

AU - Sproles, Alyssa A.

AU - Shah, Jaimin S.

AU - Köhl, Jörg

AU - Belkaid, Yasmine

AU - Wills-Karp, Marsha

PY - 2005/12/5

Y1 - 2005/12/5

N2 - 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. JEM

AB - 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. JEM

UR - http://www.scopus.com/inward/record.url?scp=28544432829&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=28544432829&partnerID=8YFLogxK

U2 - 10.1084/jem.20051506

DO - 10.1084/jem.20051506

M3 - Article

C2 - 16314437

AN - SCOPUS:28544432829

VL - 202

SP - 1549

EP - 1561

JO - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

SN - 0022-1007

IS - 11

ER -