CD160 expression defines a uniquely exhausted subset of T lymphocytes in HTLV-1 infection

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 myelopat...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2014-10, Vol.453 (3), p.379-384
Main Authors: Chibueze, Chioma Ezinne, Yoshimitsu, Makoto, Arima, Naomichi
Format: Article
Language:English
Subjects:
Antigens, CD - immunology
Flow Cytometry
GPI-Linked Proteins - immunology
Herpesvirus
HTLV-I Infections - immunology
Human T-lymphotropic virus 1
Humans
Immunologic Memory
Receptors, Immunologic - immunology
Receptors, Tumor Necrosis Factor, Member 14 - metabolism
T-Lymphocyte Subsets
T-Lymphocytes - immunology
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Summary: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.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2014.09.084