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https://www.arca.fiocruz.br/handle/icict/39054
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2021-01-08
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- INI - Artigos de Periódicos [3645]
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HIGH FREQUENCIES OF FUNCTIONALLY COMPETENT CIRCULATING TAX-SPECIFIC CD8+ T CELLS IN HUMAN T LYMPHOTROPIC VIRUS TYPE 2 INFECTION
Author
Affilliation
University College Dublin. Centre for Research in Infectious Diseases. Dublin, Ireland.
University College Dublin. Centre for Research in Infectious Diseases. Dublin, Ireland.
Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Laboratório de Pesquisa em Patogenia Viral. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Laboratório de Pesquisa em Neuroinfecções. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Laboratório de Pesquisa em Patogenia Viral. Rio de Janeiro, RJ, Brasil.
University College Dublin. National Virus Reference Laboratory. Dublin, Ireland.
University College Dublin. Centre for Research in Infectious Diseases. Dublin, Ireland.
National University of Ireland. Department of Biology. Cellular Immunology Laboratory. Maynooth, Ireland / Trinity College Dublin. St. James’s Hospital Department of Immunology. Dublin, Ireland.
University College Dublin. Centre for Research in Infectious Diseases. Dublin, Ireland / Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Laboratório de Pesquisa em Neuroinfecções. Rio de Janeiro, RJ, Brasil.
University College Dublin. Centre for Research in Infectious Diseases. Dublin, Ireland / University College Dublin. National Virus Reference Laboratory. Dublin, Ireland.
University College Dublin. Centre for Research in Infectious Diseases. Dublin, Ireland.
Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Laboratório de Pesquisa em Patogenia Viral. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Laboratório de Pesquisa em Neuroinfecções. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Laboratório de Pesquisa em Patogenia Viral. Rio de Janeiro, RJ, Brasil.
University College Dublin. National Virus Reference Laboratory. Dublin, Ireland.
University College Dublin. Centre for Research in Infectious Diseases. Dublin, Ireland.
National University of Ireland. Department of Biology. Cellular Immunology Laboratory. Maynooth, Ireland / Trinity College Dublin. St. James’s Hospital Department of Immunology. Dublin, Ireland.
University College Dublin. Centre for Research in Infectious Diseases. Dublin, Ireland / Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Laboratório de Pesquisa em Neuroinfecções. Rio de Janeiro, RJ, Brasil.
University College Dublin. Centre for Research in Infectious Diseases. Dublin, Ireland / University College Dublin. National Virus Reference Laboratory. Dublin, Ireland.
Abstract
Human T lymphotropic virus type 2 (HTLV-2) is characterized by a clinically asymptomatic persistent infection in the vast majority of infected individuals. In this study, we have characterized for the first time ex vivo specific CTL responses against the HTLV-2 Tax protein. We could detect CTL responses only against a single HLA-A*0201-restricted Tax2 epitope, comprising residues 11–19 (LLYGYPVYV), among three alleles screened. Virus-specific CTLs could be detected in most evaluated subjects, with frequencies as high as 24% of circulating CD8 T cells. The frequency of specific CTLs had a statistically significant positive correlation with proviral load levels. The majority of virus-specific CD8 T cells exhibited an effector memory/terminally differentiated phenotype, expressed high levels of cytotoxicity mediators, including perforin and granzyme B, and lysed in vitro target cells pulsed with Tax2 (11–19) synthetic peptide in a dose-dependent manner. Our findings suggest that a strong, effective CTL response may control HTLV-2 viral burden and that this may be a significant factor in maintaining persistent infection and in the prevention of disease in infected individuals.
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