%0 Journal Article
%T Is There a Role for HTLV-1-Specific CTL in Adult T-Cell Leukemia/Lymphoma?
%A Aileen G. Rowan
%A Charles R. M. Bangham
%J Leukemia Research and Treatment
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/391953
%X ATLL is an aggressive malignancy of T cells that affects about 5% of individuals infected with HTLV-1. The precise mechanism of oncogenesis is not known, but there is evidence that two regulatory viral proteins, Tax and HBZ, are involved. A high set point proviral load is associated with development of ATLL or a chronic inflammatory condition, HAM/TSP. Several lines of evidence, including HLA class 1 association studies and in vitro killing assays, indicate that cytotoxic T lymphocytes are instrumental in determining this proviral load set point. Prior studies have focused chiefly on the CTL response to the immunodominant Tax protein: efficient lysis of Tax-expressing cells inversely correlates with proviral load in nonmalignant infection. However, a recent study showed that strong binding of peptides from HBZ, but not Tax, to HLA class 1 molecules was associated with a low proviral load and a reduced risk of developing HAM/TSP, indicating an important role for HBZ-specific CTL in determining infection outcome. In comparison with nonmalignant infection, HTLV-1-specific CTLs in ATLL patients are reduced in frequency and functionally deficient. Here we discuss the nature of protective CTL responses in nonmalignant HTLV-1 infection and explore the potential of CTLs to protect against ATLL. 1. Introduction Human T-cell lymphotropic virus-1 (HTLV-1) is a retrovirus which predominantly infects CD4+ T cells, where it is reverse transcribed and integrates into host DNA. The integrated provirus can then disseminate by de novo infection of T cells via the virological synapse, or by inducing clonal expansion of the host cell. Most infected individuals do not experience any symptoms, and HTLV-1-associated disease is rarely observed in individuals with a proviral load of less than 1% of their peripheral blood mononuclear cells (PBMCs) [1]. Approximately 2¨C6% of individuals HTLV-1 develop adult T-cell leukemia/lymphoma (ATLL), and a slightly lower percentage suffer from inflammatory disorders, including HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). ATLL is a highly aggressive T-cell malignancy with a poor prognosis, and, even with standard treatment, the median survival time for clinically acute forms of the disease is measured in months [2, 3]. Chemotherapeutic intervention has had limited efficacy despite the development of drugs to specifically target ATLL cells, though some improvement has been reported combining antiviral drugs (zidovudine) and immunomodulators (such as type-1 interferon) [3¨C5]. Allogeneic hematopoietic stem cell
%U http://www.hindawi.com/journals/lrt/2012/391953/