Cellular immune response to HTLV-1

Abstract

There is strong evidence at the individual level and the population level that an efficient cytotoxic T lymphocyte (CTL) response to HTLV-1 limits the proviral load and the risk of associated inflammatory diseases such as HAM/TSP. This evidence comes from host population genetics, viral genetics, DNA expression microarrays and assays of lymphocyte function. However, until now there has been no satisfactory and rigorous means to define or to measure the efficiency of an antiviral CTL response. Recently, methods have been developed to quantify lymphocyte turnover rates in vivo and the efficiency of anti-HTLV-1 CTLs ex vivo. Data from these new techniques appear to substantiate the conclusion that variation between individual hosts in the rate at which a single CTL kills HTLV-1-infected lymphocytes is an important determinant, perhaps the decisive determinant, of the proviral load and the risk of HAM/ TSP. With these experimental data, it is becoming possible to refine, parameterize and test mathematical models of the immune control of HTLV-1, which are a necessary part of an understanding of this complex dynamic system.

Effects of valproate on Tax and HBZ expression in HTLV-1 and HAM/TSP T lymphocytes

“…[7][8][9] Those studies also demonstrated a relative stability of the HTLV-1-proviral load throughout the disease. Set-point provirus load and subsequent HAM/TSP risk are influenced by the cellular immune-response efficiency, 10 although excessive activation of HTLV-1-specific CTLs might become deleterious and contribute to central nervous system tissue damage. 4 Host-pathogen interplay is characterized by very dynamic kinetics, resulting in an equilibrium between the virus-driven clonal expansion of infected T cells 11 and tight control exerted by the immune response.…”

“…4 Host-pathogen interplay is characterized by very dynamic kinetics, resulting in an equilibrium between the virus-driven clonal expansion of infected T cells 11 and tight control exerted by the immune response. 10 Tax, a transactivator protein encoded by the pX region of the HTLV-1 genome, plays a central role in disease pathogenesis. Tax activates viral transcription and also modulates many cellular signaling pathways involved in T cell activation, cycling, apoptosis or a combination.…”

Leucémies T induites par HTLV-1

“…Elle se caractérise par le développement de paralysies spastiques 3 des membres inférieurs et de déficits sensoriels divers, conséquence des lésions d'inflammation et de démyélinisation. Cependant, les mécanismes exacts responsables de cette démyélinisation restent encore hypothétiques.…”

“…Tax stimule donc sa propre expression mais aussi par la suite l'expression des autres protéines virales telles que Gag et Env qui codent pour les protéines de structure de la particule virale (Figure 1). Cette production de protéines virales induit l'apparition d'anticorps dirigés contre Gag, Env puis Tax lors des premiers temps de l'infection [3]. Les cellules infectées sont aussi la cible d'une forte réponse immune cellulaire cytotoxique anti-Tax.…”

HTLV-I infection: A dynamic struggle between viral persistence and host immunity

“…2000; Bangham and Osame, 2005;Matsuoka and Green, 2009;Mosley et al, 2005). There is no cure or neutralising vaccine for HTLV-I, and neither is there an effective treatment available for HTLV-I-associated pathologies -infection is life-long (Bangham, 2000;Kubota et al, 2007;Mosley et al, 2005;Proietti et al, 2005).…”