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Abnormally High Levels of Virus-Infected IFN-γ+CCR4+CD4+CD25+ T Cells in a Retrovirus-Associated Neuroinflammatory Disorder.
- Source :
- PLoS ONE; 2009, Vol. 4 Issue 8, p1-14, 14p, 1 Chart, 8 Graphs
- Publication Year :
- 2009
-
Abstract
- 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<superscript>+</superscript>CD25<superscript>+</superscript>CCR4<superscript>+</superscript> 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-γ production is extraordinarily increased and IL-4, IL- 10, IL-17, and Foxp3 expression is decreased in the CD4<superscript>+</superscript>CD25<superscript>+</superscript>CCR4<superscript>+</superscript> 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-γ-producing CD4<superscript>+</superscript>CD25<superscript>+</superscript>CCR4<superscript>+</superscript>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-γ <superscript>+</superscript>CCR4<superscript>+</superscript>CD4<superscript>+</superscript>CD25<superscript>+</superscript> T cellsγthat is abnormally increased and functionally altered in this retrovirus-associated inflammatory disorder of the central nervous system. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 4
- Issue :
- 8
- Database :
- Complementary Index
- Journal :
- PLoS ONE
- Publication Type :
- Academic Journal
- Accession number :
- 57426411
- Full Text :
- https://doi.org/10.1371/journal.pone.0006517