title: CD160 expression defines a uniquely exhausted subset of T lymphocytes in HTLV-1 infection.
abstract: HTLV-1 infection is a life-long retroviral infection. Chronic viral antigenic stimulation induces persistent infection which results in a clinically asymptomatic carrier state. Only a minor proportion of infected individuals develop adult T cell leukemia/lymphoma (ATLL) or HTLV-1-associated myelopathy/tropical spastic myelopathy (HAM/TSP). This is dependent on a balance of host and genetic factors. CD8+ cytotoxic T lymphocyte function is important in the immune response against viral infection; however, the contribution of CD160 receptor associated with CD8+ T lymphocytes is unclear. Thus, we sought to decipher its role on CTL function in HTLV-1 infection. Here, we report high frequencies of CD160 on CD8+ T cells, with significantly higher levels on HTLV-1 specific CD8+ T cells. Intercepting the CD160 pathway via blockade of the receptor or its ligand, herpes virus entry mediator (HVEM) resulted in improved perforin production and CD107a degranulation of HTLV-1 specific CD8+ T cells. Analysis of the CD160-expressing CD8+ cells demonstrated a unique subset associated with a highly differentiated effector memory based on CD45RA and CCR7 co-expression, increased expression of inhibitory molecules, 2B4 and PD1. Altogether, these results suggest a role for CD160/HVEM pathway in regulating immune response against HTLV-1 infection which may prove promising in the development of immune therapies for the treatment of HTLV-1 infection and other associated disorders.
authors.affiliation: Division of Hematology and Immunology, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
authors.forename: Chioma Ezinne
authors.initials: CE
authors.lastname: Chibueze
authors.affiliation: Division of Hematology and Immunology, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan; Department of Hematology and Immunology, Kagoshima University Hospital, Kagoshima, Japan. Electronic address: myoshimi@m.kufm.kagoshima-u.ac.jp.
authors.forename: Makoto
authors.initials: M
authors.lastname: Yoshimitsu
authors.affiliation: Division of Hematology and Immunology, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan; Department of Hematology and Immunology, Kagoshima University Hospital, Kagoshima, Japan.
authors.forename: Naomichi
authors.initials: N
authors.lastname: Arima
mesh_terms: D015703:Antigens, CD / Q000276:immunology*; D005434:Flow Cytometry; D058851:GPI-Linked Proteins / Q000276:immunology; D015490:HTLV-I Infections / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D011971:Receptors, Immunologic / Q000276:immunology*; D053240:Receptors, Tumor Necrosis Factor, Member 14 / Q000378:metabolism; D016176:T-Lymphocyte Subsets; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D015703:Antigens, CD; C114505:CD160 protein, human; D058851:GPI-Linked Proteins; D011971:Receptors, Immunologic; D053240:Receptors, Tumor Necrosis Factor, Member 14; C506028:TNFRSF14 protein, human
keywords: CD160; Cell surface receptor; Cytotoxic T lymphocyte; Human T-cell lymphotropic virus-1 (HTLV-1) infection