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Role of IL-21 in HTLV-1 infections with emphasis on HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP)

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Abstract

Interleukin-21 (IL-21) enhances the survival and cytotoxic properties of cytotoxic T cells (CTLs) and exhibits essential roles in controlling chronic viral infections. HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic progressive inflammatory disease of the nervous system. The main determinant of disease progression is efficiency of the CTL response to Human T lymphotropic virus types I (HTLV-1). In this study, the expression of host IL-21 and HTLV-I Tax and proviral load (PVL) was evaluated to understand the role and mechanism of IL-21 in HTLV-1 infections and the subsequent development of HAM/TSP. A cross-sectional study was carried out on 20 HAM/TSP patients, 20 asymptomatic HTLV-1 carriers (ACs) and 20 healthy controls (HCs) to evaluate the expression of IL-21 and Tax and PVL in non-activated and phorbol myristate acetate (PMA)-ionomycin-activated peripheral blood mononuclear cells (PBMCs). The mean mRNA expression of IL-21 in the non-activated and activated PBMCs was higher (by 5–13 times) in the HAM/TSP patients than in ACs and HCs (p < 0.05); however, there was no significant difference between ACs and HCs. In contrast to the IL-21 mRNA expression, the serum level of the IL-21 protein was significantly lower in the HAM/TSP patients than in ACs and HCs (p < 0.05). Furthermore, higher expression of Tax and PVL was observed in the HAM/TSP subjects than ACs (p < 0.05). In addition, Tax gene expression was positively correlated with PVL (R = 0.595, p = 0.000) and IL-21 gene expression (R = 0.395, p = 0.021) in the HTLV-1-infected subjects. In conclusion, the increase in IL-21 mRNA expression may reflect the attempt of infected T cells to induce an appropriate antiviral response, and the decrease in IL-21 protein expression may reflect the inhibition of IL-21 mRNA translation by viral factors in favour of virus evasion and dissemination.

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Acknowledgements

The authors express their appreciation to Dr. Mahmoud Reza Azarpazhooh in the Department of Neurology, Mashhad University of Medical Sciences and Dr. Reza Faridhosseini, Dr. Bahareh Fazeli, Mr. Mehdi Felegari, Mr. Farzad MollaHosseini, Mrs. Atefe Yari for their kind assistance. This study was financially supported by Vice Chancellor for Research, Mashhad University of Medical Sciences, Mashhad, Iran.

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Authors and Affiliations

  1. Immunology Center, Inflammation and Inflammatory Diseases Research Centre, Medical School, Mashhad University of Medical Sciences, Mashhad, Iran

    Taraneh Rajaei, Houshang Rafatpanah, Narges Valizadeh & Seyed Abdolrahim Rezaee

  2. Department of Immunology, Tehran University of Medical Sciences, Tehran, Iran

    Hamid Farajifard

  3. Department of Neurology and HTLV-1 Foundation, Ghaem Hospital, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Reza Bustani

  4. Department of Medical Genetics, Institute of Medical Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran

    Bahareh Rajaei

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  1. Taraneh Rajaei
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Correspondence to Seyed Abdolrahim Rezaee.

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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: 1961).

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Informed consent was obtained from all individual participants included in the study.

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Rajaei, T., Farajifard, H., Rafatpanah, H. et al. Role of IL-21 in HTLV-1 infections with emphasis on HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Med Microbiol Immunol 206, 195–201 (2017). https://doi.org/10.1007/s00430-017-0492-3

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