Clinical Investigation for Virus-Host Interactions and its Implication in the Development of HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP).

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Human T-cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is observed only in 1-2% of HTLV-1 infected individuals. We have previously reported that HTLV-1 Tax subtype, several HLA and non-HLA genes are closely associated with the development of HAM/TSP. Based on these findings, we developed the best-fit logistic regression equation to predict the odds of HAM/TSP. We applied this equation to 181 consecutively ascertained healthy HTLV-1 carriers (HCs) and found a significant association between a high odds of HAM/TSP and two factors: brisk patellar deep tendon reflexes, which suggest latent central nervous system compromise, and flower cell (ATL cell)-like abnormal lymphocytes. Our data suggests the usefulness of our equation for detecting subclinical HAM/TSP-related neurological abnormalities. We further analyzed CD4+ and CD8+ T cells in PBMCs from HAM/TSP patients, HCs and normal uninfected controls by flow cytometry based analyses. We have used synthetic tetramers composed of HLA and its immunodominant epitope peptide to analyze Env-specific CD4+ T and Tax-specific CD8+ T cells directly from peripheral blood. Significantly higher frequency of activated and clonally expanded tetramer+CD4+ and tetramer+CD8+ T cells were observed in HAM/TSP patients than HCs, suggesting that active and continus expansion of HTLV-1 specific T cells during chronic infection play a role in the development of HAM/TSP.