title: High expression of CD244 and SAP regulated CD8 T cell responses of patients with HTLV-I associated neurologic disease.
abstract: HTLV-I-specific CD8(+) T cells have been characterized with high frequencies in peripheral blood and cerebrospinal fluid and production of proinflammatory cytokines, which contribute to central nervous system inflammation in HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). However, little is known about the differences in CD8(+) T cell activation status between asymptomatic carrier (ACs) and patients with HAM/TSP. The expression of CD244, a signaling lymphocyte activation molecule (SLAM) family receptor, was significantly higher on CD8(+) T cells in HTLV-I-infected patients, both ACs and patients with HAM/TSP, than those on healthy normal donors (NDs). Blockade of CD244 inhibited degranulation and IFN-gamma production in CD8(+) T cells of patients with HAM/TSP, suggesting that CD244 is associated with effector functions of CD8(+) T cells in patients with HAM/TSP. Moreover, SLAM-associated protein (SAP) was overexpressed in patients with HAM/TSP compared to ACs and NDs. SAP expression in Tax-specific CTLs was correlated in the HTLV-I proviral DNA loads and the frequency of the cells in HTLV-I-infected patients. SAP knockdown by siRNA also inhibited IFN-gamma production in CD8(+) T cells of patients with HAM/TSP. Thus, the CD244/SAP pathway was involved in the active regulation of CD8(+) T cells of patients with HAM/TSP, and may play roles in promoting inflammatory neurological disease.
authors.affiliation: Viral Immunology Section, Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Enose-Akahata
authors.forename: Eiji
authors.initials: E
authors.lastname: Matsuura
authors.forename: Unsong
authors.initials: U
authors.lastname: Oh
authors.forename: Steven
authors.initials: S
authors.lastname: Jacobson
mesh_terms: D015703:Antigens, CD / Q000096:biosynthesis* / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002450:Cell Communication; D015550:Cell Degranulation; D005434:Flow Cytometry; D055785:Gene Knockdown Techniques; D006801:Humans; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000378:metabolism; D019409:Interleukin-15 / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D015493:Paraparesis, Tropical Spastic / Q000276:immunology / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000096:biosynthesis* / Q000276:immunology / Q000378:metabolism; D012044:Regression Analysis; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; D000071176:Signaling Lymphocytic Activation Molecule Family
chemical_list: D015703:Antigens, CD; C084093:CD244 protein, human; D019409:Interleukin-15; D007376:Interleukin-2; D047908:Intracellular Signaling Peptides and Proteins; D011971:Receptors, Immunologic; C114953:SH2D1A protein, human; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; D000071176:Signaling Lymphocytic Activation Molecule Family; D007371:Interferon-gamma