Altered signaling lymphocytic activation molecule (SLAM) expression in HIV infection and redirection of HIV-specific responses via SLAM triggering

被引:8
作者
Meroni, L
Fusi, ML
Varchetta, S
Biasin, M
Rusconi, S
Villa, ML
De Vries, JE
Aversa, G
Galli, M
Clerici, M
机构
[1] Univ Milan, Osped Luigi Sacco, Padigl LITA, Cattedra Immunol, I-20157 Milan, Italy
[2] Univ Milan, Osped Luigi Sacco, Ist Malattie Infett, I-20157 Milan, Italy
[3] Novartis Res Inst, A-1235 Vienna, Austria
关键词
HIV; cytokines; T cell activation; immunology; SLAM;
D O I
10.1006/clim.1999.4747
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Signaling lymphocytic activation molecule (SLAM) is a transmembrane lymphocylic receptor which gets rapidly upregulated following cell activation. SLAM engagement augments T cell expansion and interferon-gamma (IFN-gamma) production independently of CD28. SLAM signaling is regulated by the SLAM-associated protein. We evaluated the expression and function of SLAM on CD4(+) and CD8(+) lymphocytes in HIV-infected individuals with either recently acquired infection (Group A) or asymptomatic HIV infection (Group B) and in healthy controls (HC). Soluble antigen (HIV env peptides and tetanus toroid)- and mitogen-stimulated proliferation and IFN-gamma and IL-10 production upon SLAM costimulation were also measured. Results showed that: (1) SLAM-expressing CD4(+) and CD8(+) lymphocytes diminish in group A patients compared to both group B patients and HC; (2) SLAM expression on CD4(+) lymphocytes is preferentially associated with the lack of CD7 on cell surface (CD4(+)CD7(-) produce IL-10 but not IFN-gamma); (3) SLAM engagement increases HIV env peptide-stimulated, but neither tetanus toxoid- nor PHA-stimulated proliferation of peripheral blood mononuclear cells (PBMC) in patients but not in HC; and (4) SLAM engagement augments IFN-gamma and reduces IL-10 production by env peptide-stimulated PBMC of HIV-infected individuals. These results demonstrate that early HIV infection results in an altered SLAM expression which correlates with a time-limited impairment of cell-mediated immunity. Furthermore, they show that triggering via SLAM potentiates HIV-specific proliferative responses with simultaneous downregulation of IL-10 and redirection of the response to TH0/TH1. (C) 1999 Academic Press.
引用
收藏
页码:276 / 284
页数:9
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