Abstract
Rationale: T-regulatory cells (Tregs) are potent immunomodulators in allergic asthma. Objectives:We evaluated the functional effects of Tregs by adoptively transferring naturally occurring CD4+CD25+ Tregs (NTregs) and CD4+CD25- inducible Tregs (iTregs) from lung and spleens of green fluorescent protein (GFP)-transgenic Balb/c mice into cockroachsensitized and -challenged mice. Methods: GFP-labeled NTregs and iTregs were adoptively transferred into cockroach-sensitized and -challenged mice. Airway hyperresponsiveness (AHR) to methacholine was examined using a single-chamber, whole-body plethysmograph and invasive tracheostomy. Measurements and Main Results: Adoptive transfer of either NTregs or iTregs from lung or spleen reversed airway inflammation and AHRto methacholine, and the effect lasted for at least 4 weeks. GFP-labeled iTregs up-regulated CD25 and forkhead-winged transcriptional factor box protein 3 and migrated to lymph node and lung. Lung CD4+CD25+ T cells isolated from each group of recipient mice were inducible costimulatory molecule-high and programmed death (PD)-1-positive; however, higher expression of PD-1 was found in the spleen iTregs (S25-) and lung iTregs (L25-) groups. Higher levels of transforming growth factor-β and IL-10 mRNA transcripts and bronchoalveolar lavage fluid IL-10 and INF-γ levels were observed in lung CD4+CD25+ cells from the L252 and S252 cell-recipient mice than from lung NTregs (L25-) and spleen NTregs (S25+) cell-recipient mice. Adoptive transfer of either cell type significantly reduced bronchoalveolar lavage fluid IL-4, IL-5, and IL-13 levels. Conclusions: Tregs reverse AHR and airway inflammation; however iTregs that differentiated into IL-10-producing CD4+ type 1 cells in the lung exert their suppressive activity likely by higher levels of transforming growth factor-β, IL-10, IFN-γ, and elevated levels of PD-1 compared with NTregs. Hence, PD-1 may be a conduit for reversing AHR by Tregs and a plausible target for treating asthma.
| Original language | English |
|---|---|
| Pages (from-to) | 211-225 |
| Number of pages | 15 |
| Journal | American Journal of Respiratory and Critical Care Medicine |
| Volume | 180 |
| Issue number | 3 |
| DOIs | |
| State | Published - Aug 1 2009 |
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All Science Journal Classification (ASJC) codes
- Critical Care and Intensive Care Medicine
- Pulmonary and Respiratory Medicine
Cite this
Naturally occurring and inducible T-regulatory cells modulating immune response in allergic asthma. / McGee, Halvor S.; Agrawal, Devendra K.
In: American Journal of Respiratory and Critical Care Medicine, Vol. 180, No. 3, 01.08.2009, p. 211-225.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Naturally occurring and inducible T-regulatory cells modulating immune response in allergic asthma
AU - McGee, Halvor S.
AU - Agrawal, Devendra K.
PY - 2009/8/1
Y1 - 2009/8/1
N2 - Rationale: T-regulatory cells (Tregs) are potent immunomodulators in allergic asthma. Objectives:We evaluated the functional effects of Tregs by adoptively transferring naturally occurring CD4+CD25+ Tregs (NTregs) and CD4+CD25- inducible Tregs (iTregs) from lung and spleens of green fluorescent protein (GFP)-transgenic Balb/c mice into cockroachsensitized and -challenged mice. Methods: GFP-labeled NTregs and iTregs were adoptively transferred into cockroach-sensitized and -challenged mice. Airway hyperresponsiveness (AHR) to methacholine was examined using a single-chamber, whole-body plethysmograph and invasive tracheostomy. Measurements and Main Results: Adoptive transfer of either NTregs or iTregs from lung or spleen reversed airway inflammation and AHRto methacholine, and the effect lasted for at least 4 weeks. GFP-labeled iTregs up-regulated CD25 and forkhead-winged transcriptional factor box protein 3 and migrated to lymph node and lung. Lung CD4+CD25+ T cells isolated from each group of recipient mice were inducible costimulatory molecule-high and programmed death (PD)-1-positive; however, higher expression of PD-1 was found in the spleen iTregs (S25-) and lung iTregs (L25-) groups. Higher levels of transforming growth factor-β and IL-10 mRNA transcripts and bronchoalveolar lavage fluid IL-10 and INF-γ levels were observed in lung CD4+CD25+ cells from the L252 and S252 cell-recipient mice than from lung NTregs (L25-) and spleen NTregs (S25+) cell-recipient mice. Adoptive transfer of either cell type significantly reduced bronchoalveolar lavage fluid IL-4, IL-5, and IL-13 levels. Conclusions: Tregs reverse AHR and airway inflammation; however iTregs that differentiated into IL-10-producing CD4+ type 1 cells in the lung exert their suppressive activity likely by higher levels of transforming growth factor-β, IL-10, IFN-γ, and elevated levels of PD-1 compared with NTregs. Hence, PD-1 may be a conduit for reversing AHR by Tregs and a plausible target for treating asthma.
AB - Rationale: T-regulatory cells (Tregs) are potent immunomodulators in allergic asthma. Objectives:We evaluated the functional effects of Tregs by adoptively transferring naturally occurring CD4+CD25+ Tregs (NTregs) and CD4+CD25- inducible Tregs (iTregs) from lung and spleens of green fluorescent protein (GFP)-transgenic Balb/c mice into cockroachsensitized and -challenged mice. Methods: GFP-labeled NTregs and iTregs were adoptively transferred into cockroach-sensitized and -challenged mice. Airway hyperresponsiveness (AHR) to methacholine was examined using a single-chamber, whole-body plethysmograph and invasive tracheostomy. Measurements and Main Results: Adoptive transfer of either NTregs or iTregs from lung or spleen reversed airway inflammation and AHRto methacholine, and the effect lasted for at least 4 weeks. GFP-labeled iTregs up-regulated CD25 and forkhead-winged transcriptional factor box protein 3 and migrated to lymph node and lung. Lung CD4+CD25+ T cells isolated from each group of recipient mice were inducible costimulatory molecule-high and programmed death (PD)-1-positive; however, higher expression of PD-1 was found in the spleen iTregs (S25-) and lung iTregs (L25-) groups. Higher levels of transforming growth factor-β and IL-10 mRNA transcripts and bronchoalveolar lavage fluid IL-10 and INF-γ levels were observed in lung CD4+CD25+ cells from the L252 and S252 cell-recipient mice than from lung NTregs (L25-) and spleen NTregs (S25+) cell-recipient mice. Adoptive transfer of either cell type significantly reduced bronchoalveolar lavage fluid IL-4, IL-5, and IL-13 levels. Conclusions: Tregs reverse AHR and airway inflammation; however iTregs that differentiated into IL-10-producing CD4+ type 1 cells in the lung exert their suppressive activity likely by higher levels of transforming growth factor-β, IL-10, IFN-γ, and elevated levels of PD-1 compared with NTregs. Hence, PD-1 may be a conduit for reversing AHR by Tregs and a plausible target for treating asthma.
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U2 - 10.1164/rccm.200809-1505OC
DO - 10.1164/rccm.200809-1505OC
M3 - Article
C2 - 19447898
AN - SCOPUS:67749139559
VL - 180
SP - 211
EP - 225
JO - American Journal of Respiratory and Critical Care Medicine
JF - American Journal of Respiratory and Critical Care Medicine
SN - 1073-449X
IS - 3
ER -