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.

Altered signaling lymphocytic activation molecule (SLAM) expression in HIV infection and redirection of HIV-specific responses via SLAM triggering / L. Meroni, M. Fusi, S. Varchetta, M. Biasin, S. Rusconi, M. Villa, J. De Vries, G. Aversa, M. Galli, M. Clerici. - In: CLINICAL IMMUNOLOGY. - ISSN 1521-6616. - 92:3(1999 Sep), pp. 276-284. [10.1006/clim.1999.4747]

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

M. Biasin;S. Rusconi;M. Galli;M. Clerici
1999-09

Abstract

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.
Cytokines; HIV; Immunology; SLAM; T cell activation
Settore MED/17 - Malattie Infettive
CLINICAL IMMUNOLOGY
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/207297
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