In vivo expression of human T-lymphotropic virus type 1 basic leucine-zipper protein generates specific CD8+ and CD4+ T-lymphocyte responses that correlate with clinical outcome

人类 T 淋巴细胞病毒 1 型碱性亮氨酸拉链蛋白的体内表达产生与临床结果相关的特异性 CD8+ 和 CD4+ T 淋巴细胞反应

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作者:Silva Hilburn, Aileen Rowan, Maria-Antonietta Demontis, Aidan MacNamara, Becca Asquith, Charles R M Bangham, Graham P Taylor

Background

The roles of the human T-lymphotropic virus type 1 (HTLV-1) basic leucine zipper (HBZ) gene are not clearly understood. We examined CD8+ and CD4+ T cell responses to HBZ and compared these with Tax responses. Method: Interferon (IFN)-γ and interleukin (IL)-2-secreting T cells were detected by enzyme-linked immunosorbent spot (ELISpot) assays of freshly isolated peripheral blood mononuclear cells (PBMCs) stimulated with synthetic HBZ or Tax peptides. Ten patients with HTLV-1-associated myelopathy (HAM) and 20 asymptomatic HTLV-1 carriers (ACs), (10 high, 10 low viral load).

Conclusion

HBZ protein is expressed in vivo in patients with HAM and in ACs. Our results are consistent with the idea that the T cell response to HBZ plays an important part in restricting HTLV-1 viral load.

Results

Of 30 study participants, 17 had detectable HBZ-specific CD4+ T cells and 12 had HBZ-specific CD8+ T cell responses. Detection of Tax-specific CD4+ T cells (IL-2- or IFN-γ-secreting) did not differ by disease status, but Tax-specific CD8+ T cell responses were more commonly detected in patients with HAM. HBZ-specific CD4+ or CD8+ T cells were less likely to be detected than Tax-specific T cells. IL-2-secreting Tax-specific CD8+ T cells, and IFN-γ-secreting Tax-specific CD4+ T cells were associated with HAM. Low viral load, asymptomatic HTLV-1 carriage was associated with IL-2-secreting CD8+ T cells specific for HBZ.

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