Altered signaling lymphocytic activation molecule (SLAM) expression in HIV infection and redirection of HIV-specific responses via SLAM triggering.
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-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 toxoid)- 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.
Meroni
L
L
Universita' di Milano, Ospedale Luigi Sacco, Via G.B. Grassi, 74, Milano, 20157, Italy.
Fusi
M L
ML
Varchetta
S
S
Biasin
M
M
Rusconi
S
S
Villa
M L
ML
De Vries
J E
JE
Aversa
G
G
Galli
M
M
Clerici
M
M
D000328:Adult; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD; D016516:CD4-CD8 Ratio; D002455:Cell Division; D016207:Cytokines / Q000096:biosynthesis / Q000187:drug effects; D015686:Gene Products, env / Q000494:pharmacology; D006023:Glycoproteins / Q000235:genetics* / Q000276:immunology / Q000502:physiology; D006678:HIV / Q000502:physiology; D015658:HIV Infections / Q000097:blood* / Q000378:metabolism; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics* / Q000276:immunology / Q000502:physiology; D007371:Interferon-gamma / Q000096:biosynthesis; D010455:Peptides / Q000494:pharmacology; D011956:Receptors, Cell Surface; D015398:Signal Transduction; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D013601:T-Lymphocytes / Q000821:virology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D016207:Cytokines; D015686:Gene Products, env; D006023:Glycoproteins; D007136:Immunoglobulins; D010455:Peptides; D011956:Receptors, Cell Surface; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D007371:Interferon-gamma