Abnormally High Levels of Virus-Infected IFN-gamma( )CCR4( )CD4( )CD25( ) T Cells in a Retrovirus-Associated Neuroinflammatory Disorder

作者：Yamano Yoshihisa^*; Araya Natsumi; Sato Tomoo; Utsunomiya Atae; Azakami Kazuko; Hasegawa Daisuke; Izumi Toshihiko; Fujita Hidetoshi; Aratani Satoko; Yagishita Naoko; Fujii Ryoji; Nishioka Kusuki; Jacobson Steven; Nakajima Toshihiro

来源：PLos One, 2009, 4(8): e6517.

DOI：10.1371/journal.pone.0006517

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( ) T Foxp3 2 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.

• 出版日期2009-8-5
• 单位河北医科大学