Virus-induced dysfunction of CD4+CD25+ T cells in patients with HTLV-I–associated neuroimmunological disease
Yoshihisa Yamano, … , Dragan A. Maric, Steven Jacobson
Yoshihisa Yamano, … , Dragan A. Maric, Steven Jacobson
Published May 2, 2005
Citation Information: J Clin Invest. 2005;115(5):1361-1368. https://doi.org/10.1172/JCI23913.
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Article Immunology

Virus-induced dysfunction of CD4+CD25+ T cells in patients with HTLV-I–associated neuroimmunological disease

Abstract

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.

Authors

Yoshihisa Yamano, Norihiro Takenouchi, Hong-Chuan Li, Utano Tomaru, Karen Yao, Christian W. Grant, Dragan A. Maric, Steven Jacobson

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Figure 2

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Lack of regulatory function in CD4+CD25+ T cells from HAM/TSP patients. ...
Lack of regulatory function in CD4+CD25+ T cells from HAM/TSP patients. A total of 1 × 105 CD4+CD25– T cells/well from HDs were labeled with CFSE. They were cultured for 6 days in the culture medium in the absence or presence of 2.5 μg/ml anti-CD3 antibody (top 2 panels). They were also cultured for 6 days in 2.5 μg/ml anti-CD3 antibody added to culture medium with 1 × 105 irradiated allogeneic CD4+CD25+ T cells from HDs or with 1 × 105 irradiated CD4+CD25+ T cells from HAM/TSP patients (bottom 2 panels). The data indicate that regulatory function in CD4+CD25+ T cells from HAM/TSP patients is reduced in comparison with that in CD4+CD25+ T cells from HDs. Failure of CD4+CD25+ T cells to suppress lymphoproliferation of activated HD cells was observed in separate experiments with cells from 4 HAM/TSP patients, while suppression of activated HD cell proliferation by allogeneic HD CD4+CD25+ T cells from 2 HDs was demonstrated.