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

In vivo fluctuation of Tax, Foxp3, CTLA-4, and GITR mRNA expression in CD4+CD25+ T cells of patients with human T-lymphotropic virus type 1-associated myelopathy

“…The transfection of the HTLV-1 tax gene into purified CD4 + CD25 + T cells from non-infected healthy donors caused a decrease in Foxp3 expression. Thus, in T cells of HAM/TSP patients, Tax transactivation might be associated with a Foxp3 reduction both in mRNA expression and protein synthesis (9). Despite the cardinal role of lymphocytes in controlling the immune response, the molecular mechanisms involved in the interaction between Foxp3 and Tax remain unknown.…”

“…The forward primer RPX-3 (5096-5115; 5'-ATCCCGTGG AGACTCCTCAA-3') and the reverse primer RPX-4+3 (7360-7338; 5'-CCAAACACGTAGACTGGGTATCC-3') were located upstream and downstream of the second splice junction site of HTLV-1 pX (tax/rex) mRNA, respectively. Primers (Invitrogen) for the amplification of Foxp3, CTLA-4, GITR, IL-10, and TGF-β mRNA have been previously described (9,22,23). We used primers for the human housekeeping gene hypoxanthine ribosyl transferase (HPRT; BiosChile IGSA, Chile) for internal calibration (24).…”

“…The main reservoir of HTLV-1 in HAM/TSP patients is the CD4 + CD25 + T-regulatory cell population (Treg cells) (9). In addition, Tax-specific inhibition of Foxp3 mRNA expression may be associated with the suppression of CD4 + CD25 + T cells that in turn might be related to the suppression of Treg function (9,10).…”

“…In addition, Tax-specific inhibition of Foxp3 mRNA expression may be associated with the suppression of CD4 + CD25 + T cells that in turn might be related to the suppression of Treg function (9,10). Foxp3 is critical for the development and function of Treg, with Foxp3 reduction and Treg dysfunction being associated with autoimmune diseases such as multiple sclerosis, myasthenia gravis, and type 1 diabetes (11)(12)(13).…”

Host Immune System Abnormalities Among Patients with Human T-Lymphotropic Virus Type 1 (HTLV-1) - Associated Disorders

“…Significant reductions in Foxp3 expression and/or Treg cell function have been observed in several human autoimmune diseases (Sakaguchi et al, 2008), suggesting that defects in Foxp3 expression and/or Treg function may precipitate the loss of immunologic tolerance. Recently, significant reductions in Foxp3 expression and Treg cell function have also been observed in CD4 + CD25 + T cells and/or CD4 + CD25 + CCR4 + T cells from patients with HAM/TSP Michaelsson et al, 2008;Oh et al, 2006;Ramirez et al, 2010;Yamano et al, 2005). Furthermore, decreased expression levels of the Treg-associated immune suppressive molecules CTLA-4 and GITR were also observed on CD4 + CD25 + T cells in HAM/TSP patients (Ramirez et al, 2010;Yamano et al, 2005).…”