title: Expression of signaling lymphocytic activation molecule-associated protein interrupts IFN-gamma production in human tuberculosis.
abstract: Production of the Th1 cytokine IFN-gamma by T cells is considered crucial for immunity against Mycobacterium tuberculosis infection. We evaluated IFN-gamma production in tuberculosis in the context of signaling molecules known to regulate Th1 cytokines. Two populations of patients who have active tuberculosis were identified, based on their T cell responses to the bacterium. High responder tuberculosis patients displayed significant M. tuberculosis-dependent T cell proliferation and IFN-gamma production, whereas low responder tuberculosis patients displayed weak or no T cell responses to M. tuberculosis. The expression of the signaling lymphocytic activation molecule (SLAM)-associated protein (SAP) on cells from tuberculosis patients was inversely correlated with IFN-gamma production in those individuals. Moreover, patients with a nonfunctional SAP gene displayed immune responses to M. tuberculosis similar to those of high responder tuberculosis patients. In contrast to SAP, T cell expression of SLAM was directly correlated with responsiveness to M. tuberculosis Ag. Our data suggest that expression of SAP interferes with Th1 responses whereas SLAM expression contributes to Th1 cytokine responses in tuberculosis. The study further suggests that SAP and SLAM might be focal points for therapeutic modulation of T cell cytokine responses in tuberculosis.
authors.affiliation: Department of Microbiology, Parasitology and Immunology, University of Buenos Aires School of Medicine, Paraguay 2155 12th Floor, Capital Federal, 1121 Buenos Aires, Argentina.
authors.forename: Virginia
authors.initials: V
authors.lastname: Pasquinelli
authors.forename: María F
authors.initials: MF
authors.lastname: Quiroga
authors.forename: Gustavo J
authors.initials: GJ
authors.lastname: Martínez
authors.forename: Liliana Castro
authors.initials: LC
authors.lastname: Zorrilla
authors.forename: Rosa M
authors.initials: RM
authors.lastname: Musella
authors.forename: María M
authors.initials: MM
authors.lastname: Bracco
authors.forename: Liliana
authors.initials: L
authors.lastname: Belmonte
authors.forename: Alejandro
authors.initials: A
authors.lastname: Malbrán
authors.forename: Leonardo
authors.initials: L
authors.lastname: Fainboim
authors.forename: Peter A
authors.initials: PA
authors.lastname: Sieling
authors.forename: Verónica E
authors.initials: VE
authors.lastname: García
mesh_terms: D000276:Adjuvants, Immunologic / Q000378:metabolism / Q000502:physiology; D000911:Antibodies, Monoclonal / Q000378:metabolism; D015703:Antigens, CD; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D002478:Cells, Cultured; D041321:Chromosomes, Human, X / Q000276:immunology; D015536:Down-Regulation / Q000276:immunology*; D006023:Glycoproteins / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D007111:Immunity, Cellular / Q000235:genetics; D007136:Immunoglobulins / Q000378:metabolism* / Q000502:physiology; D007371:Interferon-gamma / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000494:pharmacology; D018664:Interleukin-12 / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D008232:Lymphoproliferative Disorders / Q000235:genetics / Q000276:immunology; D009169:Mycobacterium tuberculosis / Q000276:immunology; D011956:Receptors, Cell Surface; D012720:Severity of Illness Index; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D014376:Tuberculosis / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D015854:Up-Regulation / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D002352:Carrier Proteins; D006023:Glycoproteins; D007136:Immunoglobulins; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D011956:Receptors, Cell Surface; C114953:SH2D1A protein, human; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D018664:Interleukin-12; D007371:Interferon-gamma