Activation pathways implicate anti-HLA-DP and anti-LFA-1 antibodies as lead candidates for intervention in chronic berylliosis

Yuan K. Chou, David M. Edwards, Andrew D. Weinberg, Arthur Vandenbark, Brian L. Kotzin, Andrew P. Fontenot, Gregory G. Burrows

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

CD4+ T cells play a key role in granulomatous inflammation in the lung of patients with chronic beryllium disease. The goal of this study was to characterize activation pathways of beryllium-responsive bronchoalveolar lavage (BAL) CD4+ T cells from chronic beryllium disease patients to identify possible therapeutic interventional strategies. Our results demonstrate that in the presence of APCs, beryllium induced strong proliferation responses of BAL CD4+ T cells, production of superoptimal concentrations of secreted proinflammatory cytokines, IFN-γ, TNF-α,and IL-2, and up-regulation of numerous T cell surface markers that would promote T-T Ag presentation. Ab blocking experiments revealed that anti-HLA-DP or anti-LFA-1 Ab strongly reduced proliferation responses and cytokine secretion by BAL CD4 + T cells. In contrast, anti-HLA-DR or anti-OX40 ligand Ab mainly affected beryllium-induced proliferation responses with little impact on cytokines other than IL-2, thus implying that nonproliferating BAL CD4 + T cells may still contribute to inflammation. Blockade with CTLA4-Ig had a minimal effect on proliferation and cytokine responses, confirming that activation was independent of B7/CD28 costimulation. These results indicate a prominent role for HLA-DP and LFA-1 in BAL CD4+ T cell activation and further suggest that specific Abs to these molecules could serve as a possible therapy for chronic beryllium disease.

Original languageEnglish (US)
Pages (from-to)4316-4324
Number of pages9
JournalJournal of Immunology
Volume174
Issue number7
StatePublished - Apr 1 2005

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Berylliosis
HLA-DP Antigens
Lymphocyte Function-Associated Antigen-1
Bronchoalveolar Lavage
T-Lymphocytes
Antibodies
Beryllium
Cytokines
Chronic Disease
Interleukin-2
OX40 Ligand
HLA-DR Antigens
Pneumonia
Up-Regulation
Inflammation

ASJC Scopus subject areas

  • Immunology

Cite this

Chou, Y. K., Edwards, D. M., Weinberg, A. D., Vandenbark, A., Kotzin, B. L., Fontenot, A. P., & Burrows, G. G. (2005). Activation pathways implicate anti-HLA-DP and anti-LFA-1 antibodies as lead candidates for intervention in chronic berylliosis. Journal of Immunology, 174(7), 4316-4324.

Activation pathways implicate anti-HLA-DP and anti-LFA-1 antibodies as lead candidates for intervention in chronic berylliosis. / Chou, Yuan K.; Edwards, David M.; Weinberg, Andrew D.; Vandenbark, Arthur; Kotzin, Brian L.; Fontenot, Andrew P.; Burrows, Gregory G.

In: Journal of Immunology, Vol. 174, No. 7, 01.04.2005, p. 4316-4324.

Research output: Contribution to journalArticle

Chou, YK, Edwards, DM, Weinberg, AD, Vandenbark, A, Kotzin, BL, Fontenot, AP & Burrows, GG 2005, 'Activation pathways implicate anti-HLA-DP and anti-LFA-1 antibodies as lead candidates for intervention in chronic berylliosis', Journal of Immunology, vol. 174, no. 7, pp. 4316-4324.
Chou, Yuan K. ; Edwards, David M. ; Weinberg, Andrew D. ; Vandenbark, Arthur ; Kotzin, Brian L. ; Fontenot, Andrew P. ; Burrows, Gregory G. / Activation pathways implicate anti-HLA-DP and anti-LFA-1 antibodies as lead candidates for intervention in chronic berylliosis. In: Journal of Immunology. 2005 ; Vol. 174, No. 7. pp. 4316-4324.
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