A tax on luxury: HTLV-I infection of CD4+CD25+ Tregs

Abstract

Almost a quarter of a century ago, Oldstone and colleagues proposed that infection of cells by noncytopathic viruses may lead to an alteration of the cells' ability to produce certain products or perform certain tasks, i.e., inhibition of "luxury function." In this issue of the JCI, this topic has been revisited by Yamano et al., who demonstrate that human T cell lymphotropic virus type I (HTLV-I) infection of CD4(+)CD25(+) Tregs in patients with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) results in a decrease in FOXP3 mRNA and protein expression. This leads to the inability of HTLV-I-infected CD4(+)CD25(+) Tregs to inhibit the proliferation of CD4(+)CD25(-) Tregs, due to the effect of the HTLV-I tax gene. Defects in the Treg population could be responsible for the large numbers of virus-specific T cells and occurrence of lymphoproliferation and inflammatory autoimmune disease in HAM/TSP patients.

Figure 1

CD4⁺CD25⁺ Tregs limit the proliferation of stimulated CD4⁺CD25⁻ T cells. Studies have shown that lack of these regulatory cells can lead to lymphoproliferative disease and autoimmunity. In this issue of the JCI, Yamano et al. (2) report that CD4⁺CD25⁺ T cells infected with HTLV-I (from HAM/TSP patients) have decreased levels of FOXP3 expression and lack the ability to suppress CD4⁺CD25⁻ T cell proliferation. CD4⁺CD25⁺ T cells transfected with the HTLV-I tax gene also have decreased levels of FOXP3 expression and lack the ability to suppress the proliferation of stimulated CD4⁺CD25⁻ T cells.