Goon Peter K C, Igakura Tadahiko, Hanon Emmanuel, Mosley Angelina J, Barfield Anna, Barnard Amanda L, Kaftantzi Lambrini, Tanaka Yuetsu, Taylor Graham P, Weber Jonathan N, Bangham Charles R M
Department of Immunology, Imperial College London, London, United Kingdom.
J Immunol. 2004 Feb 1;172(3):1735-43. doi: 10.4049/jimmunol.172.3.1735.
CD4(+) T cells predominate in early lesions in the CNS in the inflammatory disease human lymphotropic T cell virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP), but the pathogenesis of the disease remains unclear and the HTLV-I-specific CD4(+) T cell response has been little studied. We quantified the IFN-gamma-producing HTLV-I-specific CD4(+) T cells, in patients with HAM/TSP and in asymptomatic carriers with high proviral load, to test two hypotheses: that HAM/TSP patients and asymptomatic HTLV-I carriers with a similar proviral load differ in the immunodominance hierarchy or the total frequency of specific CD4(+) T cells, and that HTLV-I-specific CD4(+) T cells are preferentially infected with HTLV-I. The strongest CD4(+) T cell response in both HAM/TSP patients and asymptomatic carriers was specific to Env. This contrasts with the immunodominance of Tax in the HTLV-I-specific CD8(+) T cell response. The median frequency of HTLV-I-specific IFN-gamma(+) CD4(+) T cells was 25-fold greater in patients with HAM/TSP (p = 0.0023, Mann-Whitney) than in asymptomatic HTLV-I carriers with a similar proviral load. Furthermore, the frequency of CD4(+) T cells infected with HTLV-I (expressing Tax protein) was significantly greater (p = 0.0152, Mann-Whitney) among HTLV-I-specific cells than CMV-specific cells. These data were confirmed by quantitative PCR for HTLV-I DNA. We conclude that the high frequency of specific CD4(+) T cells was associated with the disease HAM/TSP, and did not simply reflect the higher proviral load that is usually found in HAM/TSP patients. Finally, we conclude that HTLV-I-specific CD4(+) T cells are preferentially infected with HTLV-I.
在炎症性疾病人类嗜T淋巴细胞病毒I型（HTLV-I）相关脊髓病/热带痉挛性截瘫（HAM/TSP）中，CD4(+) T细胞在中枢神经系统早期病变中占主导地位，但该病的发病机制仍不清楚，对HTLV-I特异性CD4(+) T细胞反应的研究很少。我们对HAM/TSP患者和前病毒载量高的无症状携带者中产生干扰素-γ的HTLV-I特异性CD4(+) T细胞进行了定量，以检验两个假设：即具有相似前病毒载量的HAM/TSP患者和无症状HTLV-I携带者在免疫优势等级或特异性CD4(+) T细胞的总频率上存在差异，以及HTLV-I特异性CD4(+) T细胞优先感染HTLV-I。HAM/TSP患者和无症状携带者中最强的CD4(+) T细胞反应均针对Env。这与HTLV-I特异性CD8(+) T细胞反应中Tax的免疫优势形成对比。HAM/TSP患者中HTLV-I特异性干扰素-γ(+) CD4(+) T细胞的中位频率比具有相似前病毒载量的无症状HTLV-I携带者高25倍（p = 0.0023，曼-惠特尼检验）。此外，在HTLV-I特异性细胞中，感染HTLV-I（表达Tax蛋白）的CD4(+) T细胞频率明显高于巨细胞病毒特异性细胞（p = 0.0152，曼-惠特尼检验）。这些数据通过HTLV-I DNA定量PCR得到证实。我们得出结论，特异性CD4(+) T细胞的高频率与HAM/TSP疾病相关，并非简单反映HAM/TSP患者中通常较高的前病毒载量。最后，我们得出结论，HTLV-I特异性CD4(+) T细胞优先感染HTLV-I。
