Pentoxifylline inhibits granzyme B and perforin expression following T-lymphocyte activation by anti-CD3 antibody

被引:16
作者
Hoskin, DW
Phu, T
Makrigiannis, AP
机构
[1] Dept. of Microbiol. and Immunology, Faculty of Medicine, Dalhousie University, Halifax
来源
INTERNATIONAL JOURNAL OF IMMUNOPHARMACOLOGY | 1996年 / 18卷 / 11期
基金
加拿大自然科学与工程研究理事会;
关键词
pentoxifylline; killer lymphocyte; granzyme B; perforin; Fas ligand;
D O I
10.1016/S0192-0561(96)00069-0
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Pentoxifylline (PTX), a methylxanthine derivative, is known to inhibit the production of the Thl cytokines interleukin-2, tumour necrosis factor-alpha and interferon-gamma. Because these cytokines play an important role in promoting the development of cell-mediated immunity, we hypothesized that PTX would also interfere with the generation of cytotoxic effector cells in response to an immunological stimulus. In this study we used a mouse model system to investigate the effect of PTX on the induction of non-specific killer lymphocytes by anti-CD3 monoclonal antibody. Anti-CD3-induced T-cell proliferation and the generation of anti-CD3-activated killer (AK) cells was inhibited in a dose-dependent fashion by PTX (25-100 mu g/ml). The inhibitory effect of PTX could not be attributed to a defect in the recognition/adhesion phase of cytolysis because AK cells generated in the presence of PTX conjugated normally with P815 tumour target cells. However, AK cell expression of the cytoplasmic granule-associated cytolytic effector molecules granzyme B and perforin was markedly reduced when AK cells were induced in the presence of PTX. In contrast, PTX had no effect on AK cell expression of Fas ligand, a cell-surface cytolytic effector molecule which is involved in granule-independent cytotoxicity. PTX thus has a profound inhibitory effect in vitro on the induction of granule-dependent cytolytic effector mechanisms in a mouse model system. (C) 1997 International Society for Immunopharmacology.
引用
收藏
页码:623 / 631
页数:9
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