SERIAL ANALYSIS OF GENE EXPRESSION IN CD8+ T CELLS ISOLATED FROM HUMAN T-CELL LYMPHOTROPIC VIRUS TYPE 1 INFECTED PATIENTS

BM14

Malta, TM (1,2),  Silva, IT (2,3); Pinheiro, DG (2,3); Panepucci, RA (2,3); Azevedo, R (2); Nicolete, LDF (1,2); Santos, ARD (2); Takayanagui, OM (3); Covas, DT (2,3); Kashima, S (1,2,3)

(1) Faculdade de Ciências Farmacêuticas de Ribeirão Preto (2) Hemocentro de Ribeirão Preto, Brasil, Brasil;(3) Faculdade de Medicina de Ribeirão Preto – USP, Brasil

Human T cell lymphotropic virus type 1 (HTLV-1) infection is associated with two distinct clinical pathologies. About 2–3% of infected people develop an aggressive T-cell tumor, adult T cell lymphoma/leukaemia (ATLL) and another 2–3% develop chronic inflammatory diseases, of which the best known is HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Ninety-five percent of infected people remain life-long asymptomatic carriers of the virus. The mechanisms involved in HTLV-1 related diseases are not well elucidated, but host factors are an essential part in HAM/TSP pathogenesis. CD8⁺ cytotoxic T lymphocytes (CTL) have an important function in the immune response against the HTLV-1 and so in the risk of HAM/TSP. In the present study, we compared gene expression profile of CD8⁺ T cells among non-infected individuals, asymptomatic (HAC) and HAM/TSP patients using Serial Analysis of Gene Expression (SAGE). HAC group was composed by pooled samples (n=4) with low proviral load (CPV), while HAM/TSP group showed high CPV (n=4). SAGE analysis of 51,017, 62,432 and 60,620 tags from control, HAC and HAM/TSP groups respectively, allowed identification of approximately 12,000 different transcripts in each library. We identified around 900 genes differentially expressed between control group and HAC or HAM/TSP. However, only 300 genes were identified between HAC and HAM/TSP groups. The expression profile revealed the presence of highly frequent transcripts related to regulation of transcription, surface antigen and adhesion molecules, apoptosis and antigen processing and presentation. This study represents the first extensive serial analysis of gene expression of CD8+T cells in this infection and will contribute to the identification of novel genes involved in cellular and molecular events associated to HTLV-1 infection and related diseases.