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Lack of recall response to Tax in ATL and HAM/TSP patients but not in asymptomatic carriers of human T-cell leukemia virus type 1
Journal article   Open access   Peer reviewed

Lack of recall response to Tax in ATL and HAM/TSP patients but not in asymptomatic carriers of human T-cell leukemia virus type 1

Sharrón L Manuel, Mohit Sehgal, John Connolly, George Makedonas, Zafar K Khan, Jay Gardner, Michael R Betts and Pooja Jain
Journal of clinical immunology, v 33(7), pp 1223-1239
Oct 2013
DOI: https://doi.org/10.1007/s10875-013-9918-x
PMID: 23888327
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1007/s10875-013-9918-xView
Published, Version of Record (VoR) Open

Abstract

Humans Middle Aged Transcriptome Asymptomatic Diseases Human T-lymphotropic virus 1 - growth & development Viral Load Leukemia-Lymphoma, Adult T-Cell - immunology Young Adult Chemokine CCL3 - genetics Adult Chemokine CCL3 - metabolism Female Human T-lymphotropic virus 1 - immunology Cytokines - genetics Paraparesis, Tropical Spastic - immunology Gene Products, tax - immunology Cytokines - metabolism Lymphocyte Activation Gene Expression Regulation Programmed Cell Death 1 Receptor - metabolism CD8-Positive T-Lymphocytes - virology Adolescent Lymphocyte Count Aged CD8-Positive T-Lymphocytes - immunology Programmed Cell Death 1 Receptor - genetics Cytotoxicity, Immunologic
The immunopathogenic mechanisms responsible for debilitating neurodegenerative and oncologic diseases associated with human T-cell leukemia virus type 1 (HTLV-1) are not fully understood. Quality of cytotoxic T lymphocytes (CTLs) is being increasingly associated with the outcome of persistent HTLV-1 infection. In this respect, a patient cohort (from HTLV-1 endemic region) consisting of seronegative controls (controls), asymptomatic carriers (ACs), and patients with adult T-cell leukemia (ATL) or HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP) was analyzed for CD8(+) T cells polyfunctionality in response to the viral antigen Tax. Compared to ACs, ATL and HAM/TSP patients had lower frequency and polyfunctionality of CTLs in response to Tax suggesting dysfunction of CD8(+) T cells in these individuals. As an underlying mechanism, programmed death-1 (PD-1) receptor was found to be highly unregulated in Tax-responsive as well as total CD8(+) T cells from ATL and HAM/TSP but not from ACs and directly correlated with the lack of polyfunctionality in these individuals. Further, PD-1 expression showed a direct whereas MIP-1α expression had an indirect correlation with the proviral load providing new insights about the immunopathogenesis of HTLV-associated diseases. Additionally, we identified key cytokine signatures defining the immune activation status of clinical samples by the luminex assay. Collectively, our findings suggest that reconstitution of fully functional CTLs, stimulation of MIP-1α expression, and/or blockade of the PD-1 pathway are potential approaches for immunotherapy / therapeutic vaccine against HTLV-mediated diseases.

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Domestic collaboration
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Web of Science research areas
Immunology
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