期刊
PARASITE IMMUNOLOGY
卷 28, 期 8, 页码 373-385出版社
BLACKWELL PUBLISHING
DOI: 10.1111/j.1365-3024.2006.00836.x
关键词
B7; CD28; CD40; Echinococcus multilocularis; macrophage
One of the most important immunopathological consequence of intraperitoneal alveolar echinococcosis (AE) in the mouse is suppression of T cell-mediated immune responses. We investigated whether and how intraperitoneal macrophages (MOs) are, respectively, implicated as antigen-presenting cells (APCs). In a first step we showed that peritoneal MOs from infected mice (AE-MOs) exhibited a reduced ability to present a conventional antigen (chicken ovalbumin, C-Ova) to specific responder lymph node T cells. In a subsequent step, AE-MOs as well as naive MOs (positive control) proved their ability to uptake and process C-Ova fluorescein isthiocyanate (FITC). Furthermore, in comparison with naive MOs, the surface expression of Ia molecules was up-regulated on AE-MOs at the early stage of infection, suggesting that AE-MOs provide the first signal via the antigen-Ia complex. To study the accessory activity of MOs, AE-MOs obtained at the early and late stages of infection were found to decrease Con A-induced proliferation of peritoneal naive T cells as well as of AE-sensitized peritoneal T cells, in contrast to stimulation with naive MOs. The status of accessory molecules was assessed by analysing the expression level of costimulatory molecules on AE-MOs, with naive MOs as controls. It was found that B7-1 (CD80) and B7-2 (CD86) expression remained unchanged, whereas CD40 was down-regulated and CD54 (= ICAM-1) was slightly up-regulated. In a leucocyte reaction of AE-MOs with naive or AE-T cells, both types of T cells increased their proliferative response when CD28 - the ligand of B7 receptors - was exposed to anti-CD28 in cultures. Conversely to naive MOs, pulsing of AE-MOs with agonistic anti-CD40 did not even partially restore their costimulatory activity and failed to increase naive or AE-T cell proliferation. Neutralizing anti-B7-1, in combination with anti-B7-2, reduced naive and AE-T cell proliferation, whereas anti-CD40 treatment of naive MOs increased their proliferative response to Con A. These results point at the key role of B7 receptors as accessory molecules and the necessity of the integrity of CD40-expression by naive MOs to improve their accessory activity. Taken together, the obstructed presenting-activity of AE-MOs appeared to trigger an unresponsiveness of T cells, contributing to the suppression of their clonal expansion during the chronic phase of AE-infection.
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