Virus-induced dysfunction of CD4+CD25+ T cells in patients with HTLV-I-associated neuroimmunological disease.
CD4(+)CD25(+) Tregs are important in the maintenance of immunological self tolerance and in the prevention of autoimmune diseases. As the CD4(+)CD25(+) T cell population in patients with human T cell lymphotropic virus type I-associated (HTLV-I-associated) myelopathy/tropical spastic paraparesis (HAM/TSP) has been shown to be a major reservoir for this virus, it was of interest to determine whether the frequency and function of CD4(+)CD25(+) Tregs in HAM/TSP patients might be affected. In these cells, both mRNA and protein expression of the forkhead transcription factor Foxp3, a specific marker of Tregs, were lower than those in CD4(+)CD25(+) T cells from healthy individuals. The virus-encoded transactivating HTLV-I tax gene was demonstrated to have a direct inhibitory effect on Foxp3 expression and function of CD4(+)CD25(+) T cells. This is the first report to our knowledge demonstrating the role of a specific viral gene product (HTLV-I Tax) on the expression of genes associated with Tregs (in particular, foxp3) resulting in inhibition of Treg function. These results suggest that direct human retroviral infection of CD4(+)CD25(+) T cells may be associated with the pathogenesis of HTLV-I-associated neurologic disease.
Yamano
Yoshihisa
Y
Viral Immunology Section, Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, Maryland 20892, USA.
Takenouchi
Norihiro
N
Li
Hong-Chuan
HC
Tomaru
Utano
U
Yao
Karen
K
Grant
Christian W
CW
Maric
Dragan A
DA
Jacobson
Steven
S
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology*; D016207:Cytokines / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D051858:Forkhead Transcription Factors; D016356:Gene Products, tax / Q000235:genetics / Q000378:metabolism; D015490:HTLV-I Infections / Q000276:immunology*; D015368:Human T-lymphotropic virus 1 / Q000276:immunology*; D006801:Humans; D015493:Paraparesis, Tropical Spastic / Q000276:immunology / Q000378:metabolism / Q000821:virology*; D015375:Receptors, Interleukin-2 / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000821:virology; D014162:Transfection
D016207:Cytokines; D004268:DNA-Binding Proteins; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D016356:Gene Products, tax; D015375:Receptors, Interleukin-2