The roles of acquired and innate immunity in human T-cell leukemia virus type 1-mediated diseases

Mari Kannagi,Shuichi Kinpara,Atae Utsunomiya,Atsuhiko Hasegawa,Ayako Takamori

doi:10.3389/fmicb.2012.00323

Abstract

Human T-cell leukemia virus type 1 (HTLV-1) causes adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis in small subsets of HTLV-1 carriers. HTLV-1-specific T-cell responses play critical roles in anti-viral and anti-tumor host defense during HTLV-1 infections. Some HTLV-1 carriers exhibit selective loss or anergy of HTLV-1-specific T-cells at an asymptomatic stage. This is also observed in ATL patients and may therefore be an underlying risk factor of ATL in combination with elevated proviral loads. HTLV-1-specific T-cells often recognize the viral oncoprotein Tax, indicating expression of Tax protein in vivo, although levels of HTLV-1 gene expression are known to be very low. A type-I interferon (IFN) response can be induced by HTLV-1-infected cells and suppresses HTLV-1 expression in vitro, suggesting a role of type-I IFN response in viral suppression and pathogenesis in vivo. Both acquired and innate immune responses control the status of HTLV-1-infected cells and could be the important determinants in the development of HTLV-1-mediated malignant and inflammatory diseases.

Highlights

Human T-lymphotropic virus type I (HTLV-1) causes adult T-cell leukemia (ATL) (Hinuma et al, 1981; Uchiyama, 1997) and HTLV1-associated myelopathy/tropical spastic paraparesis (HAM/TSP; Gessain et al, 1985; Osame et al, 1986) in a subset of infected individuals
In a different rat model of Human T-cell leukemia virus type 1 (HTLV-1) infection, oral HTLV-1 infection induced HTLV-1-specific T-cell tolerance and caused an elevation in the proviral load, while re-immunization of these rats resulted in the recovery of HTLV-1-specific Tcell responses and caused a reduction in the proviral loads (Hasegawa et al, 2003; Komori et al, 2006).patients carrying HTLV-1 developed ATL after liver transplantation, when immunosuppressants were administered (Kawano et al, 2006; Suzuki et al, 2006).These findings suggest that HTLV-1-specific T-cells, especially Tax-specific cytotoxic T lymphocyte (CTL), play important roles in anti-tumor and anti-viral surveillance in HTLV-1 infection
SELECTIVE IMPAIRMENT OF HTLV-1-SPECIFIC T-CELLS IN EARLY STAGES OF ATL, A POTENTIAL RISK FOR ATL We previously identified some major epitopes recognized by HTLV-1-specific CTLs presented by human leukocyte antigen (HLA)-A2, -A11, or -A24 through analysis of CTLs collected from ATL patients after HSCT or collected from HAM/TSP patients (Kannagi et al, 1992; Harashima et al, 2004, 2005).The identification of these epitopes allowed us to monitor HTLV-1-specific CTLs and analyze their functions ex vivo by using antigen/HLA tetrameric complexes

Summary

Introduction

Human T-lymphotropic virus type I (HTLV-1) causes adult T-cell leukemia (ATL) (Hinuma et al, 1981; Uchiyama, 1997) and HTLV1-associated myelopathy/tropical spastic paraparesis (HAM/TSP; Gessain et al, 1985; Osame et al, 1986) in a subset of infected individuals. While ATL is a malignant lymphoproliferative disease, HAM/TSP presents as a chronic inflammatory neurodegenerative disease. It is not known how one virus can cause two vastly different diseases. Since no disease-specific difference among HTLV-1 strains have been identified (Daenke et al, 1990; Kinoshita et al, 1991), the different pathogenic consequences must be attributed to host factors. The two diseases usually occur in different populations of HTLV-1 carriers. Identification of the determinant factors may allow the prediction of disease risks and the development of prophylactic and therapeutic strategies

Objectives

Findings

Conclusion