Cellular and humoral autoreactivity in idiopathic pulmonary fibrosis

Carol A. Feghali-Bostwick, Christopher G. Tsai, Vincent G. Valentine, Stephen Kantrow, Michael W. Stoner, Joseph M. Pilewski, Aneal Gadgil, M. Patricia George, Kevin F. Gibson, Augustine M K Choi, Naftali Kaminski, Yingze Zhang, Steven R. Duncan

Research output: Contribution to journalArticle

111 Citations (Scopus)

Abstract

Idiopathic pulmonary fibrosis (IPF) is a morbid, refractory lung disorder with an unknown pathogenesis. To investigate potential adaptive immune mechanisms in IPF, we compared phenotypes and effector functions of peripheral CD4 T cells, autoantibody production, and proliferative responses of pulmonary hilar lymph node CD4 T cells to autologous lung extracts from afflicted patients and normals. Our results show that greater proportions of peripheral CD4 T lymphocytes in IPF subjects expressed MHC class II and CD154 (CD40L), and they more frequently elaborated TGF-β1, IL-10, and TNF-α. Abnormal CD4 T cell clonal expansions were found in all IPF patients, and 82% of these subjects also had IgG autoantibodies against cellular Ags. IPF lung extracts stimulated proliferations of autologous CD4 T cells, unlike preparations from normals or those with other lung diseases, and the IPF proliferative responses were enhanced by repeated cycles of stimulation. Thus, CD4 T cells from IPF patients have characteristics typical of cell-mediated pathologic responses, including augmented effector functions, provision of facultative help for autoantibody production, oligoclonal expansions, and proliferations driven by an Ag present in diseased tissues. Recognition that an autoreactive immune process is present in IPF can productively focus efforts toward identifying the responsible Ag, and implementing more effective therapies.

Original languageEnglish (US)
Pages (from-to)2592-2599
Number of pages8
JournalJournal of Immunology
Volume179
Issue number4
StatePublished - Aug 15 2007
Externally publishedYes

Fingerprint

Idiopathic Pulmonary Fibrosis
T-Lymphocytes
Autoantibodies
Lung
CD40 Ligand
Interleukin-10
Lung Diseases
Immunoglobulin G
Lymph Nodes
Phenotype

ASJC Scopus subject areas

  • Immunology

Cite this

Feghali-Bostwick, C. A., Tsai, C. G., Valentine, V. G., Kantrow, S., Stoner, M. W., Pilewski, J. M., ... Duncan, S. R. (2007). Cellular and humoral autoreactivity in idiopathic pulmonary fibrosis. Journal of Immunology, 179(4), 2592-2599.

Cellular and humoral autoreactivity in idiopathic pulmonary fibrosis. / Feghali-Bostwick, Carol A.; Tsai, Christopher G.; Valentine, Vincent G.; Kantrow, Stephen; Stoner, Michael W.; Pilewski, Joseph M.; Gadgil, Aneal; George, M. Patricia; Gibson, Kevin F.; Choi, Augustine M K; Kaminski, Naftali; Zhang, Yingze; Duncan, Steven R.

In: Journal of Immunology, Vol. 179, No. 4, 15.08.2007, p. 2592-2599.

Research output: Contribution to journalArticle

Feghali-Bostwick, CA, Tsai, CG, Valentine, VG, Kantrow, S, Stoner, MW, Pilewski, JM, Gadgil, A, George, MP, Gibson, KF, Choi, AMK, Kaminski, N, Zhang, Y & Duncan, SR 2007, 'Cellular and humoral autoreactivity in idiopathic pulmonary fibrosis', Journal of Immunology, vol. 179, no. 4, pp. 2592-2599.
Feghali-Bostwick CA, Tsai CG, Valentine VG, Kantrow S, Stoner MW, Pilewski JM et al. Cellular and humoral autoreactivity in idiopathic pulmonary fibrosis. Journal of Immunology. 2007 Aug 15;179(4):2592-2599.
Feghali-Bostwick, Carol A. ; Tsai, Christopher G. ; Valentine, Vincent G. ; Kantrow, Stephen ; Stoner, Michael W. ; Pilewski, Joseph M. ; Gadgil, Aneal ; George, M. Patricia ; Gibson, Kevin F. ; Choi, Augustine M K ; Kaminski, Naftali ; Zhang, Yingze ; Duncan, Steven R. / Cellular and humoral autoreactivity in idiopathic pulmonary fibrosis. In: Journal of Immunology. 2007 ; Vol. 179, No. 4. pp. 2592-2599.
@article{0e8126295f5f448c95097bb4c5c766dd,
title = "Cellular and humoral autoreactivity in idiopathic pulmonary fibrosis",
abstract = "Idiopathic pulmonary fibrosis (IPF) is a morbid, refractory lung disorder with an unknown pathogenesis. To investigate potential adaptive immune mechanisms in IPF, we compared phenotypes and effector functions of peripheral CD4 T cells, autoantibody production, and proliferative responses of pulmonary hilar lymph node CD4 T cells to autologous lung extracts from afflicted patients and normals. Our results show that greater proportions of peripheral CD4 T lymphocytes in IPF subjects expressed MHC class II and CD154 (CD40L), and they more frequently elaborated TGF-β1, IL-10, and TNF-α. Abnormal CD4 T cell clonal expansions were found in all IPF patients, and 82{\%} of these subjects also had IgG autoantibodies against cellular Ags. IPF lung extracts stimulated proliferations of autologous CD4 T cells, unlike preparations from normals or those with other lung diseases, and the IPF proliferative responses were enhanced by repeated cycles of stimulation. Thus, CD4 T cells from IPF patients have characteristics typical of cell-mediated pathologic responses, including augmented effector functions, provision of facultative help for autoantibody production, oligoclonal expansions, and proliferations driven by an Ag present in diseased tissues. Recognition that an autoreactive immune process is present in IPF can productively focus efforts toward identifying the responsible Ag, and implementing more effective therapies.",
author = "Feghali-Bostwick, {Carol A.} and Tsai, {Christopher G.} and Valentine, {Vincent G.} and Stephen Kantrow and Stoner, {Michael W.} and Pilewski, {Joseph M.} and Aneal Gadgil and George, {M. Patricia} and Gibson, {Kevin F.} and Choi, {Augustine M K} and Naftali Kaminski and Yingze Zhang and Duncan, {Steven R.}",
year = "2007",
month = "8",
day = "15",
language = "English (US)",
volume = "179",
pages = "2592--2599",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "4",

}

TY - JOUR

T1 - Cellular and humoral autoreactivity in idiopathic pulmonary fibrosis

AU - Feghali-Bostwick, Carol A.

AU - Tsai, Christopher G.

AU - Valentine, Vincent G.

AU - Kantrow, Stephen

AU - Stoner, Michael W.

AU - Pilewski, Joseph M.

AU - Gadgil, Aneal

AU - George, M. Patricia

AU - Gibson, Kevin F.

AU - Choi, Augustine M K

AU - Kaminski, Naftali

AU - Zhang, Yingze

AU - Duncan, Steven R.

PY - 2007/8/15

Y1 - 2007/8/15

N2 - Idiopathic pulmonary fibrosis (IPF) is a morbid, refractory lung disorder with an unknown pathogenesis. To investigate potential adaptive immune mechanisms in IPF, we compared phenotypes and effector functions of peripheral CD4 T cells, autoantibody production, and proliferative responses of pulmonary hilar lymph node CD4 T cells to autologous lung extracts from afflicted patients and normals. Our results show that greater proportions of peripheral CD4 T lymphocytes in IPF subjects expressed MHC class II and CD154 (CD40L), and they more frequently elaborated TGF-β1, IL-10, and TNF-α. Abnormal CD4 T cell clonal expansions were found in all IPF patients, and 82% of these subjects also had IgG autoantibodies against cellular Ags. IPF lung extracts stimulated proliferations of autologous CD4 T cells, unlike preparations from normals or those with other lung diseases, and the IPF proliferative responses were enhanced by repeated cycles of stimulation. Thus, CD4 T cells from IPF patients have characteristics typical of cell-mediated pathologic responses, including augmented effector functions, provision of facultative help for autoantibody production, oligoclonal expansions, and proliferations driven by an Ag present in diseased tissues. Recognition that an autoreactive immune process is present in IPF can productively focus efforts toward identifying the responsible Ag, and implementing more effective therapies.

AB - Idiopathic pulmonary fibrosis (IPF) is a morbid, refractory lung disorder with an unknown pathogenesis. To investigate potential adaptive immune mechanisms in IPF, we compared phenotypes and effector functions of peripheral CD4 T cells, autoantibody production, and proliferative responses of pulmonary hilar lymph node CD4 T cells to autologous lung extracts from afflicted patients and normals. Our results show that greater proportions of peripheral CD4 T lymphocytes in IPF subjects expressed MHC class II and CD154 (CD40L), and they more frequently elaborated TGF-β1, IL-10, and TNF-α. Abnormal CD4 T cell clonal expansions were found in all IPF patients, and 82% of these subjects also had IgG autoantibodies against cellular Ags. IPF lung extracts stimulated proliferations of autologous CD4 T cells, unlike preparations from normals or those with other lung diseases, and the IPF proliferative responses were enhanced by repeated cycles of stimulation. Thus, CD4 T cells from IPF patients have characteristics typical of cell-mediated pathologic responses, including augmented effector functions, provision of facultative help for autoantibody production, oligoclonal expansions, and proliferations driven by an Ag present in diseased tissues. Recognition that an autoreactive immune process is present in IPF can productively focus efforts toward identifying the responsible Ag, and implementing more effective therapies.

UR - http://www.scopus.com/inward/record.url?scp=34848884629&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34848884629&partnerID=8YFLogxK

M3 - Article

C2 - 17675522

AN - SCOPUS:34848884629

VL - 179

SP - 2592

EP - 2599

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 4

ER -