Interaction of perforin and granzyme B and HTLV-1 viral factors is associated with ATL development

Document Type: Original Article

Authors

1 Immunology Research Center, Inflammation and Inflammatory Diseases Division, Mashhad University of Medical Sciences, Mashhad, Iran

2 Hematology Department, Ghaem Hospital, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

3 Hematology Department, Imam Reza Hospital, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

Abstract

Objective(s): Human T cell leukaemia virus type 1 (HTLV-1) is associated with adult T cell leukaemia (ATL), a malignant lymphoproliferative disease that infects CD4 T cells. It is not clear why the majority of HTLV-1-infected individuals remain asymptomatic carries (ACs) and a minority develop ATL. Cellular immune response has a critical role in ATL and destroys malignant and HTLV-1-infected cells. Perforin and granzyme have important functional roles in apoptosis and destruction of infected cells. In the present study we examined the role of perforin and granzyme in ATL patients and ACs.
Materials and Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from ATL patients and ACs by using Ficoll-hypaque density centrifugation. RNA was extracted and cDNA was synthesized. A real-time PCR TaqMan method was designed and optimized for evaluation of perforin, granzyme, tax, and HBZ gene expression. HTLV-1 proviral load (PVL) was quantified in patients with ATL and ACs.
Results: The mRNA expression of tax and HBZ was significantly higher in ATL patients than ACs (P=0.011 and P=0.0001,respectively). The HTLV-1 PVL was higher in ATL patients compared to with AC group (P=0.015). There was a significant increase in perforin gene expression in ACs compared with ATL patients (P=0.002).  Furthermore, the expression of granzyme was also higher in ACs compared with ATL patients, and significant differences were observed between the two groups (P=0.036).
Conclusion: Low expression of perforin and granzyme in ATL patients seems to influence the efficiency of CTL function and destruction of HTLV-1-infected cells, which might contribute to the disease pathogenesis.

Keywords


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