Evaluation of granzyme B and perforin-expressing CD8+T-lymphocytes from HTLV-1-infected patients with HAM/TSP

Abstract

Background: HTLV -1 was the first human retrovirus described and is classically associated with adult T-cell leukemia/ lymphoma (ATLL) and HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). HAM/TSP is a chronic and progressive inflammatory disease of the central nervous system and your immunopathogenic mechanisms are not completely understood. The role of cytotoxic T-lymphocytes (CTLs) in the pathogenesis of this disease is still undefined. In this study we evaluated the cytotoxic potential of cytotoxic T-lymphocytes from HTLV-1-infected patients with HAM/TSP. Methods: Assays immunophenotyping by flow cytometry were conducted to assess granzyme B (GrzB) and perforin (Perf) expression in cytotoxic T-lymphocytes. We analyzed 13 uninfected subjects (controls) and 43 HTLV-1- infected patients - 18 without myelopathy (asymptomatic-ASS) and 25 with HAM/TSP. Infected patients showed an increased proportion of cytotoxic T-lymphocytes. Results: The proportion CD8+GrzB+ cells was four times higher in HTLV-1-infected patients (33.2%) compared to uninfected volunteers (8.4%, P=0.0009). The frequency of cells expressing perforin presented similar between groups (P=0.19). However, the percentage of CD8+ cells containing granzyme B and perforin was eight times higher in infected individuals (0.9% - 6.8%, P=0.006), suggesting an increased cytotoxic potential. The ASS and HAM/TSP groups showed similar frequencies of CD8+GrzB+ and/or Perf+ (P>0.05). No significant differences were observed in these cytotoxic mediators expression between the two infected groups studied. Conclusion: These preliminary findings suggest that cytotoxic potential of CD8+ T cells is not different between ASS and HAM/TSP HTLV-1-infected groups. Further studies will be conducted in an attempt to clarify these questions.