Human T cell lymphotropic virus type I (HTLV-I)-specific CD4+ T cells:: Immunodominance hierarchy and preferential infection with HTLV-I
Human T cell lymphotropic virus type I (HTLV-I)-specific CD4+ T cells:: Immunodominance hierarchy and preferential infection with HTLV-I
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DOI：
10.4049/jimmunol.172.3.1735
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发表时间：
2004-02-01
影响因子：
4.4
通讯作者：
Bangham, CRM
中科院分区：
文献类型：
--
作者：
Goon, PKC;Igakura, T;Bangham, CRM
CD4(+) T细胞在早期病变中占主导地位，在炎症性疾病人类淋巴细胞T细胞病毒I型(HTLV-I)相关性脊髓病/热带痉挛性截瘫(HAM/TSP)的中枢神经系统中占主导地位，但该疾病的发病机制仍不清楚，并且HTLV-I特异性CD4(+) T细胞反应的研究很少。我们对 HAM/TSP 患者和高原病毒载量的无症状携带者中产生 IFN-γ 的 HTLV-I 特异性 CD4(+) T 细胞进行了定量，以检验两个假设：HAM/TSP 患者和具有相似原病毒载量的无症状 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，并且 HTLV-I 特异性CD4(+) T细胞优先被HTLV-I感染。 HAM/TSP 患者和无症状携带者中最强的 CD4(+) T 细胞反应是针对 Env 的。这与Tax在HTLV-I特异性CD8(+) T细胞反应中的免疫优势形成对比。 HAM/TSP 患者中 HTLV-I 特异性 IFN-γ(+) CD4(+) T 细胞的中位频率比具有相似原病毒载量的无症状 HTLV-I 携带者高 25 倍（p = 0.0023，Mann-Whitney）。此外，HTLV-I特异性细胞中感染HTLV-I（表达Tax蛋白）的CD4（+）T细胞的频率显着高于CMV特异性细胞（p = 0.0152，Mann-Whitney）。这些数据通过 HTLV-I DNA 的定量 PCR 得到证实。我们的结论是，特异性 CD4(+) T 细胞的高频率与 HAM/TSP 疾病相关，并且不仅仅反映了 HAM/TSP 患者中通常发现的较高前病毒载量。最后，我们得出结论，HTLV-I特异性CD4(+) T细胞优先被HTLV-I感染。
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.