Abnormally high levels of virus-infected IFN-gamma+ CCR4+ CD4+ CD25+ T cells in a retrovirus-associated neuroinflammatory disorder.
BACKGROUND:Human T-lymphotropic virus type 1 (HTLV-1) is a human retrovirus associated with both HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), which is a chronic neuroinflammatory disease, and adult T-cell leukemia (ATL). The pathogenesis of HAM/TSP is known to be as follows:...
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doaj-c59f67a458cc487fb04def28dae29ebe2020-11-25T02:47:26ZengPublic Library of Science (PLoS)PLoS ONE1932-62032009-08-0148e651710.1371/journal.pone.0006517Abnormally high levels of virus-infected IFN-gamma+ CCR4+ CD4+ CD25+ T cells in a retrovirus-associated neuroinflammatory disorder.Yoshihisa YamanoNatsumi ArayaTomoo SatoAtae UtsunomiyaKazuko AzakamiDaisuke HasegawaToshihiko IzumiHidetoshi FujitaSatoko ArataniNaoko YagishitaRyoji FujiiKusuki NishiokaSteven JacobsonToshihiro NakajimaBACKGROUND:Human T-lymphotropic virus type 1 (HTLV-1) is a human retrovirus associated with both HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), which is a chronic neuroinflammatory disease, and adult T-cell leukemia (ATL). The pathogenesis of HAM/TSP is known to be as follows: HTLV-1-infected T cells trigger a hyperimmune response leading to neuroinflammation. However, the HTLV-1-infected T cell subset that plays a major role in the accelerated immune response has not yet been identified. PRINCIPAL FINDINGS:Here, we demonstrate that CD4(+)CD25(+)CCR4(+) T cells are the predominant viral reservoir, and their levels are increased in HAM/TSP patients. While CCR4 is known to be selectively expressed on T helper type 2 (Th2), Th17, and regulatory T (Treg) cells in healthy individuals, we demonstrate that IFN-gamma production is extraordinarily increased and IL-4, IL-10, IL-17, and Foxp3 expression is decreased in the CD4(+)CD25(+)CCR4(+) T cells of HAM/TSP patients as compared to those in healthy individuals, and the alteration in function is specific to this cell subtype. Notably, the frequency of IFN-gamma-producing CD4(+)CD25(+)CCR4(+)Foxp3(-) T cells is dramatically increased in HAM/TSP patients, and this was found to be correlated with disease activity and severity. CONCLUSIONS:We have defined a unique T cell subset--IFN-gamma(+)CCR4(+)CD4(+)CD25(+) T cells--that is abnormally increased and functionally altered in this retrovirus-associated inflammatory disorder of the central nervous system.http://europepmc.org/articles/PMC2715877?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yoshihisa Yamano Natsumi Araya Tomoo Sato Atae Utsunomiya Kazuko Azakami Daisuke Hasegawa Toshihiko Izumi Hidetoshi Fujita Satoko Aratani Naoko Yagishita Ryoji Fujii Kusuki Nishioka Steven Jacobson Toshihiro Nakajima |
spellingShingle |
Yoshihisa Yamano Natsumi Araya Tomoo Sato Atae Utsunomiya Kazuko Azakami Daisuke Hasegawa Toshihiko Izumi Hidetoshi Fujita Satoko Aratani Naoko Yagishita Ryoji Fujii Kusuki Nishioka Steven Jacobson Toshihiro Nakajima Abnormally high levels of virus-infected IFN-gamma+ CCR4+ CD4+ CD25+ T cells in a retrovirus-associated neuroinflammatory disorder. PLoS ONE |
author_facet |
Yoshihisa Yamano Natsumi Araya Tomoo Sato Atae Utsunomiya Kazuko Azakami Daisuke Hasegawa Toshihiko Izumi Hidetoshi Fujita Satoko Aratani Naoko Yagishita Ryoji Fujii Kusuki Nishioka Steven Jacobson Toshihiro Nakajima |
author_sort |
Yoshihisa Yamano |
title |
Abnormally high levels of virus-infected IFN-gamma+ CCR4+ CD4+ CD25+ T cells in a retrovirus-associated neuroinflammatory disorder. |
title_short |
Abnormally high levels of virus-infected IFN-gamma+ CCR4+ CD4+ CD25+ T cells in a retrovirus-associated neuroinflammatory disorder. |
title_full |
Abnormally high levels of virus-infected IFN-gamma+ CCR4+ CD4+ CD25+ T cells in a retrovirus-associated neuroinflammatory disorder. |
title_fullStr |
Abnormally high levels of virus-infected IFN-gamma+ CCR4+ CD4+ CD25+ T cells in a retrovirus-associated neuroinflammatory disorder. |
title_full_unstemmed |
Abnormally high levels of virus-infected IFN-gamma+ CCR4+ CD4+ CD25+ T cells in a retrovirus-associated neuroinflammatory disorder. |
title_sort |
abnormally high levels of virus-infected ifn-gamma+ ccr4+ cd4+ cd25+ t cells in a retrovirus-associated neuroinflammatory disorder. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2009-08-01 |
description |
BACKGROUND:Human T-lymphotropic virus type 1 (HTLV-1) is a human retrovirus associated with both HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), which is a chronic neuroinflammatory disease, and adult T-cell leukemia (ATL). The pathogenesis of HAM/TSP is known to be as follows: HTLV-1-infected T cells trigger a hyperimmune response leading to neuroinflammation. However, the HTLV-1-infected T cell subset that plays a major role in the accelerated immune response has not yet been identified. PRINCIPAL FINDINGS:Here, we demonstrate that CD4(+)CD25(+)CCR4(+) T cells are the predominant viral reservoir, and their levels are increased in HAM/TSP patients. While CCR4 is known to be selectively expressed on T helper type 2 (Th2), Th17, and regulatory T (Treg) cells in healthy individuals, we demonstrate that IFN-gamma production is extraordinarily increased and IL-4, IL-10, IL-17, and Foxp3 expression is decreased in the CD4(+)CD25(+)CCR4(+) T cells of HAM/TSP patients as compared to those in healthy individuals, and the alteration in function is specific to this cell subtype. Notably, the frequency of IFN-gamma-producing CD4(+)CD25(+)CCR4(+)Foxp3(-) T cells is dramatically increased in HAM/TSP patients, and this was found to be correlated with disease activity and severity. CONCLUSIONS:We have defined a unique T cell subset--IFN-gamma(+)CCR4(+)CD4(+)CD25(+) T cells--that is abnormally increased and functionally altered in this retrovirus-associated inflammatory disorder of the central nervous system. |
url |
http://europepmc.org/articles/PMC2715877?pdf=render |
work_keys_str_mv |
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