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

Authors:
Yamano Y, Takenouchi N, Li HC, Tomaru U, Yao K, Grant CW, Maric DA and Jacobson S
In:
Source: J Clin Invest
Publication Date: (2005)
Issue: 115(5): 1361-1368
Research Area:
Immunotherapy / Hematology
Cells used in publication:
T cell, human peripheral blood unstim.
Species: human
Tissue Origin: blood
T cell, human stim.
Species: human
Tissue Origin: blood
Platform:
Nucleofectorâ„¢ I/II/2b
Experiment
CD4+/CD25+ and CD4+/CD25- T cells were isolated from patients with human T cell lymphotropic virus type I-associated (HTLVI-associated) myelopathy/tropical spastic paraparesis and normal controls. These cells were nucleofected with plasmids expressing HTLV1-env or HTLV1-tax and the effect on fox3p expression was measured.
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.