Ligation of human CD4 interferes with antigen-induced activation of primary T cells

被引:17
作者
Marschner, S
Hünig, T
Cambier, JC
Finkel, TH
机构
[1] Univ Colorado, Hlth Sci Ctr, Integrated Dept Immunol, Natl Jewish Med & Res Ctr, Denver, CO 80206 USA
[2] Univ Wurzburg, Inst Virol & Immunol, D-97078 Wurzburg, Germany
[3] Childrens Hosp Philadelphia, Div Rheumatol, Philadelphia, PA 19104 USA
关键词
CD4; gp120; T cell activation; antigen; tailless CD4;
D O I
10.1016/S0165-2478(02)00028-7
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 CD4 molecule functions to enhance T cell activation when it is co-aggregated with the T cell receptor for antigen (TCR) by MHC class II antigenic peptide complexes. However, independent ligation of CD4 has been shown to negatively effect signaling through the TCR in vitro. The interaction between the HIV-1 envelope glycoprotein gp120 and CD4 is a central event in the pathogenesis of AIDS and may contribute to immune deficiency via both direct and indirect mechanisms, including lytic infection of T cells and induction of CD4 signaling events resulting in apoptosis and anergy. Analysis of the consequences of interactions between CD4 and gp120 have yielded contradictory results presumably because most of these studies have focused on T cell clones of questionable relevance to the in vivo target of the virus. Here, we analyzed the effects of CD4 ligation on freshly isolated cells of human CD4 transgenic mice, and show that huCD4 preligation, in the absence of human CXCR4, has all inhibitory effect oil both early and late T cell activation events. CD4 signaling negatively regulates the response to antigen, as well as to anti-TCR mAb. In addition, we show here that this negative signal requires the cytoplasmic tail of CD4. These results suggest that in HIV infected patients the interaction of gp120 with CD4 induces unresponsiveness of CD4+ T cells to subsequent activation by antigen. U 2002 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:131 / 139
页数:9
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