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

Luca Meroni, Maria Luisa Fusi, Stefania Varchetta, Mara Biasin, Stefano Rusconi, Maria Luisa Villa, Jan E. De Vries, Gregorio Aversa, Massimo Galli, Mario Clerici

Research output: Contribution to journalArticle

Abstract

Signaling lymphocytic activation molecule (SLAM) is a transmembrane lymphocytic receptor which gets rapidly upregulated following cell activation. SLAM engagement augments T cell expansion and interferon-gamma (IFN-γ) 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 toxoid)- and mitogen-stimulated proliferation and IFN-γ 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-γ); (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-γ 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.

Original languageEnglish
Pages (from-to)276-284
Number of pages9
JournalClinical Immunology
Volume92
Issue number3
DOIs
Publication statusPublished - Sep 1999

Keywords

  • Cytokines
  • HIV
  • Immunology
  • SLAM
  • T cell activation

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Pathology and Forensic Medicine

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