Self-presentation of beryllium by BAL CD4+ T cells

T cell-T cell interactions and their potential role in chronic beryllium disease

Andrew P. Fontenot, David M. Edwards, Yuan K. Chou, Douglas G. Mack, Dorian LaTocha, Arthur Vandenbark, Gregory G. Burrows

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Chronic beryllium disease (CBD) is characterized pathologically by granulomatous inflammation in the lung, composed of a large core of epithelioid cells surrounded by a dense shell of CD4+ T cells. Using beryllium-specific CD4+ T cell lines derived from the bronchoalveolar lavage (BAL) fluid of CBD patients, we show that purified CD4+ T cells produced significant amounts of IFN-γ and TNF-α upon exposure to beryllium in the absence of antigen-presenting cells (APC). However, unlike BAL T cells stimulated by beryllium in the presence of APC, self-presentation by BAL T cells did not induce detectable IL-2 production, and in its absence these activated T cells die from programmed cell death. Resting BAL CD4+ T cells constitutively express high levels of HLA-DP, lymphocyte function-associated antigen 1 (LFA-1) and ICAM-3. When stimulated with beryllium/APC, the adhesion molecule ICAM-1 was up-regulated, as well as several costimulation molecules including CD28, OX-40 (CD134), 4-1-BB (CD137) and B7-1 (CD80). Notably, CD28 was not up-regulated during self-presentation by BAL T cells, and these cells do not express OX-40L, suggesting that lack of appropriate costimulation was responsible for programmed cell death observed upon beryllium self-presentation. Restricting anti-MHC class II mAb completely eliminated beryllium-induced T cell proliferation during self-presentation and significantly reduced IFN-γ and TNF-α production. Our data demonstrate for the first time that self-presentation by BAL T cells in response to beryllium can occur ex vivo, in the absence of professional APC, with a specific dependence on T cell-expressed MHC class II molecules and exogenous IL-2 for survival.

Original languageEnglish (US)
Pages (from-to)930-939
Number of pages10
JournalEuropean Journal of Immunology
Volume36
Issue number4
DOIs
StatePublished - Apr 2006

Fingerprint

Berylliosis
Beryllium
Bronchoalveolar Lavage
Cell Communication
Chronic Disease
T-Lymphocytes
Antigen-Presenting Cells
Interleukin-2
Cell Death
HLA-DP Antigens
Epithelioid Cells
Lymphocyte Function-Associated Antigen-1
Bronchoalveolar Lavage Fluid
Cell Adhesion Molecules
Intercellular Adhesion Molecule-1

Keywords

  • Chronic beryllium disease
  • Inflammation
  • Lung
  • T lymphocytes

ASJC Scopus subject areas

  • Immunology

Cite this

Self-presentation of beryllium by BAL CD4+ T cells : T cell-T cell interactions and their potential role in chronic beryllium disease. / Fontenot, Andrew P.; Edwards, David M.; Chou, Yuan K.; Mack, Douglas G.; LaTocha, Dorian; Vandenbark, Arthur; Burrows, Gregory G.

In: European Journal of Immunology, Vol. 36, No. 4, 04.2006, p. 930-939.

Research output: Contribution to journalArticle

Fontenot, Andrew P. ; Edwards, David M. ; Chou, Yuan K. ; Mack, Douglas G. ; LaTocha, Dorian ; Vandenbark, Arthur ; Burrows, Gregory G. / Self-presentation of beryllium by BAL CD4+ T cells : T cell-T cell interactions and their potential role in chronic beryllium disease. In: European Journal of Immunology. 2006 ; Vol. 36, No. 4. pp. 930-939.
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AB - Chronic beryllium disease (CBD) is characterized pathologically by granulomatous inflammation in the lung, composed of a large core of epithelioid cells surrounded by a dense shell of CD4+ T cells. Using beryllium-specific CD4+ T cell lines derived from the bronchoalveolar lavage (BAL) fluid of CBD patients, we show that purified CD4+ T cells produced significant amounts of IFN-γ and TNF-α upon exposure to beryllium in the absence of antigen-presenting cells (APC). However, unlike BAL T cells stimulated by beryllium in the presence of APC, self-presentation by BAL T cells did not induce detectable IL-2 production, and in its absence these activated T cells die from programmed cell death. Resting BAL CD4+ T cells constitutively express high levels of HLA-DP, lymphocyte function-associated antigen 1 (LFA-1) and ICAM-3. When stimulated with beryllium/APC, the adhesion molecule ICAM-1 was up-regulated, as well as several costimulation molecules including CD28, OX-40 (CD134), 4-1-BB (CD137) and B7-1 (CD80). Notably, CD28 was not up-regulated during self-presentation by BAL T cells, and these cells do not express OX-40L, suggesting that lack of appropriate costimulation was responsible for programmed cell death observed upon beryllium self-presentation. Restricting anti-MHC class II mAb completely eliminated beryllium-induced T cell proliferation during self-presentation and significantly reduced IFN-γ and TNF-α production. Our data demonstrate for the first time that self-presentation by BAL T cells in response to beryllium can occur ex vivo, in the absence of professional APC, with a specific dependence on T cell-expressed MHC class II molecules and exogenous IL-2 for survival.

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