In:
European Journal of Immunology, Wiley, Vol. 36, No. 4 ( 2006-04), p. 930-939
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.
Type of Medium:
Online Resource
ISSN:
0014-2980
,
1521-4141
DOI:
10.1002/eji.200526075
Language:
English
Publisher:
Wiley
Publication Date:
2006
detail.hit.zdb_id:
120108-6
detail.hit.zdb_id:
1491907-2
