title: HTLV-1 specific CD8+ T cell function augmented by blockade of 2B4/CD48 interaction in HTLV-1 infection.
abstract: CD8+ T cell response is important in the response to viral infections; this response though is regulated by inhibitory receptors. Expression of inhibitory receptors has been positively correlated with CD8+ T cell exhaustion; the consequent effect of simultaneous blockade of these inhibitory receptors on CD8+ T cell response in viral infections have been studied, however, the role of individual blockade of receptor-ligand pair is unclear. 2B4/CD48 interaction is involved in CD8+T cell regulation, its signal transducer SAP (signaling lymphocyte activation molecule (SLAM)-associated protein) is required for stimulatory function of 2B4/CD244 on lymphocytes hence, we analyzed 2B4/CD244 (natural killer cell receptor) and SAP (signaling lymphocyte activation molecule(SLAM)-associated protein) on total CD8+ and HTLV-1 specific CD8+T cells in HTLV-1 infection and the effect of blockade of interaction with ligand CD48 on HTLV-1 specific CD8+ T cell function. We observed a high expression of 2B4/CD244 on CD8+ T cells relative to uninfected and further upregulation on HTLV-1 specific CD8+ T cells. 2B4+ CD8+ T cells exhibited more of an effector and terminally differentiated memory phenotype. Blockade of 2B4/CD48 interaction resulted in improvement in function via perforin expression and degranulation as measured by CD107a surface mobilization on HTLV-1 specific CD8+ T cells. In the light of these findings, we thus propose an inhibitory role for 2B4/CD48 interaction on CD8+T cell function.
authors: Division of Hematology and Immunology, Center for Chronic Viral Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors: Chibueze Chioma
authors: CC
authors: Ezinne
authors: Division of Hematology and Immunology, Center for Chronic Viral Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan ; Department of Hematology and Immunology, Kagoshima University Hospital, Kagoshima, Japan.
authors: Makoto
authors: M
authors: Yoshimitsu
authors: Department of Medicine, University of the West Indies, Mona, Kingston, Jamaica.
authors: Yohann
authors: Y
authors: White
authors: Division of Hematology and Immunology, Center for Chronic Viral Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan ; Department of Hematology and Immunology, Kagoshima University Hospital, Kagoshima, Japan.
authors: Naomichi
authors: N
authors: Arima
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000276:immunology*; D000071178:CD48 Antigen; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D002454:Cell Differentiation / Q000276:immunology; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology*; D015490:HTLV-I Infections / Q000276:immunology* / Q000473:pathology; D015368:Human T-lymphotropic virus 1 / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D008297:Male; D008875:Middle Aged; D054353:Perforin / Q000276:immunology; D011971:Receptors, Immunologic / Q000276:immunology*; D000071176:Signaling Lymphocytic Activation Molecule Family
chemical_list: D015703:Antigens, CD; C084093:CD244 protein, human; D000071178:CD48 Antigen; C000604065:CD48 protein, human; D011971:Receptors, Immunologic; D000071176:Signaling Lymphocytic Activation Molecule Family; D054353:Perforin