One of the prominent features of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is the excessive recruitment of leukocytes to the central nervous system (CNS), which leads to an inflammatory response—with chemokines and their receptors playing the main role in this recruitment. The aim of the study was to examine the relation of CXCR1 and CXCR2, both of which are involved in the trafficking of lymphocytes into the CNS, with the outcome of HTLV-1 infection. The mRNA levels of CXCR1 and CXCR2 were examined in peripheral blood mononuclear cells (PBMCs) of HAM/TSP patients, HTLV-1 asymptomatic carriers (ACs), and healthy controls (HCs). Furthermore, the frequency of CD4+ and CD8+ T cells expressing CXCR1 and CXCR2 was evaluated in the studied groups. The results of the present study showed a substantial increase in the mean mRNA expression of CXCR2 in the HAM/TSP patients compared to the HCs and ACs (p < 0.001). A positive correlation was also found between PVL and CXCR2 mRNA expression in the total population of HTLV-1-infected subjects (R = 0.526, p < 0.001). Moreover, the percentage of CD8+ CXCR2-expressing cells was higher in HAM/TSP patients compared to ACs and HCs (p < 0.05, p < 0.01, respectively). Although the percentage of CD4+ CXCR2-expressing cells was higher in HAM/TSP patients than in ACs and HCs, a significant difference was only found between HAM/TSP patients and HCs (p < 0.05). No significant difference in the CXCR1 mRNA expression was observed in the studied groups. The frequency of the CD8+ CXCR1- and CD4+ CXCR1-expressing cells was significantly lower in HAM/TSP patients than in ACs and HCs (p < 0.001 and p < 0.01, respectively). In conclusion, the high frequency of CXCR2 CD8+ T cells and the high levels of CXCR2 mRNA expression in HAM/TSP patients are associated with disease pathogenesis, while the high frequencies of CXCR1 T cells in ACs might suggest that these cells act as effector CD8 T cells and are involved in controlling the viral spread and modulation of the immune response.
HTLV-1 HAM/TSP CXCR1 CXCR2
This is a preview of subscription content, log in to check access.
This study was financially supported by Vice Chancellor for Research, Mashhad University of Medical Sciences, Mashhad, Iran.
Compliance with ethical standards
Conflict of interest
There is no conflict of interest for this study.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee. The study was approved by ethics committee of Mashhad University of Medical sciences, Mashhad (No. 89659).
Informed consent was obtained from all individual participants included in the study.
Bangham CR (2000) The immune response to HTLV-I. Curr Opin Immunol 12:397–402. (doi: S0952-7915(00)00107-2 [pii])CrossRefPubMedGoogle Scholar
Goncalves DU, Proietti FA, Barbosa-Stancioli EF et al (2008) HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) inflammatory network. Inflamm Allergy Drug Targets 7:98–107CrossRefPubMedGoogle Scholar
Chuntharapai A, Lee J, Hébert CA, Kim KJ (1994) Monoclonal antibodies detect different distribution patterns of IL-8 receptor A and IL-8 receptor B on human peripheral blood leukocytes. J Immunol 153:5682–5688PubMedGoogle Scholar
Bieganowska K, Höllsberg P, Buckle GJ et al (1999) Direct analysis of viral-specific CD8 + T cells with soluble HLA-A2/Tax11-19 tetramer complexes in patients with human T cell lymphotropic virus-associated myelopathy. J Immunol 162:1765–1771PubMedGoogle Scholar
Glabinski a R, Tani M, Strieter RM et al (1997) Synchronous synthesis of alpha- and beta-chemokines by cells of diverse lineage in the central nervous system of mice with relapses of chronic experimental autoimmune encephalomyelitis. Am J Pathol 150:617–630PubMedPubMedCentralGoogle Scholar
Chuntharapai A, Kim KJ (1995) Regulation of the expression of IL-8 receptor A/B by IL-8: possible functions of each receptor. J Immunol 155:2587–2594PubMedGoogle Scholar
Sabroe I, Williams TJ, Hébert CA, Collins PD (1997) Chemoattractant cross-desensitization of the human neutrophil IL-8 receptor involves receptor internalization and differential receptor subtype regulation. J Immunol 158:1361–1369PubMedGoogle Scholar
Mori N, Mukaida N, Ballard DW et al (1998) Human T-cell leukemia virus type I Tax transactivates human interleukin 8 gene through acting concurrently on AP-1 and nuclear factor-kappa B-like sites. Cancer Res 58:3993–4000PubMedGoogle Scholar