Loss of the ex vivo but not the reinducible CD8+ T-cell response to Tax in human T-cell leukemia virus type 1-infected patients with adult T-cell leukemia/lymphoma

被引:55
作者
Arnulf, B
Thorel, M
Poirot, Y
Tamouza, R
Boulanger, E
Jaccard, A
Oksenhendler, E
Hermine, O
Pique, C
机构
[1] Hop St Louis, Inst Univ Hematol, CNRS, UPR 9051, F-75010 Paris, France
[2] Hop Necker Enfants Malad, Serv Hematol, Paris, France
[3] Hop Necker Enfants Malad, CNRS, UMR 8603, Paris, France
[4] Hop St Louis, Lab Immunol & Histocompatibil, Paris, France
[5] Hop St Louis, INSERM, U396, Paris, France
[6] Hop St Louis, Dept Immunohematol Clin, Paris, France
[7] Ctr Hosp Univ Limoges, Serv Hematol Clin, F-87042 Limoges, France
关键词
retrovirus; leukemia; CTL;
D O I
10.1038/sj.leu.2403176
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Human T-cell leukemia virus type 1 (HTLV-1) causes adult T-cell leukemia/lymphoma (ATLL) and HTLV-1-associated myelopathy (HAM). In asymptomatic carriers and HAM patients, HTLV-1 infection leads to a vigorous cytotoxic T-cell (CTL) response mainly directed to the regulatory Tax protein. In contrast, initial studies showed that anti-HTLV-1 CTL activities were not reproductively detected in ATLL patients, neither ex vivo, nor after in vitro restimulation. To better understand this discrepancy, we explored the anti-HTLV-1 CD8+ T-cell response of eight ATLL patients by using in vitro restimulated or freshly isolated CD8+ T cells. In all the ATLL patients, we found that mitogenic activation allowed the induction of CD8+ T cells able to lyse autologous HTLV-1-infected cells and/or to produce IFNgamma in response to Tax peptides. In contrast, only a minority of the patients possessed CD8+ cells able to respond ex vivo to the same epitopes. These findings indicate that although a restimulatable anti-HTLV-1 CTL activity persists during ATLL, the specific ex vivo response is not constantly maintained. This provides definitive evidence that the CD8+ T-cell response to HTLV-1 is affected by ATLL development and reveals that a major defect concerns the generation and/or the functionality of CD8+ effectors.
引用
收藏
页码:126 / 132
页数:7
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