DOUBLE-NEGATIVE T-CELLS FROM MRL-LPR/LPR MICE MEDIATE CYTOLYTIC ACTIVITY WHEN TRIGGERED THROUGH ADHESION MOLECULES AND CONSTITUTIVELY EXPRESS PERFORIN GENE

被引:54
作者
HAMMOND, DM [1 ]
NAGARKATTI, PS [1 ]
GOTE, LR [1 ]
SETH, A [1 ]
HASSUNEH, MR [1 ]
NAGARKATTI, M [1 ]
机构
[1] VIRGINIA POLYTECH INST & STATE UNIV, DEPT BIOL, DIV MICROBIOL & IMMUNOL, BLACKSBURG, VA 24061 USA
关键词
D O I
10.1084/jem.178.6.2225
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The lpr gene induces in mice, accumulation of large numbers of CD4-CD8- (double negative [DN]) T lymphocytes which bear adhesion molecules not characteristic of normal resting T cells. These cells fail to acquire interleukin 2 (IL-2) receptors, produce IL-2, and proliferate when activated with mitogens or monoclonal antibodies (mAbs) against the T cell receptor (TCR). Because of these poor functions in vitro, the nature and significance of DN T cells in the autoimmune disease process is not clear. In the current study, we describe a surprising finding that mAbs against CD3-TCR-alpha/beta complex can strongly trigger the lytic activity of the DN T cells to induce redirected lysis of Fc receptor-positive targets. Similar redirected lysis was also inducible using mAbs against CD44 and gp90MEL-14, molecules involved in the binding of lymphocytes to endothelial cells. The spontaneous cytotoxic potential of the DN T cells was further corroborated by demonstrating that the lpr DN T cells constitutively transcribed perforin gene but failed to express granzyme A. The current study suggests that DN T cells are capable of mediating lysis of autologous cells bearing the specific ligands for adhesion molecules involved in the signaling of cytotoxicity. These findings provide a novel insight into the functional significance of DN T cells in lpr mice and their potential role in the pathogenesis of autoimmune disease.
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页码:2225 / 2230
页数:6
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