Accumulation of human T lymphotropic virus type I-infected T cells in the salivary glands of patients with human T lymphotropic virus type I-associated Sj�gren's syndrome

Abstract

Objective. To clarify the involvement of human T lymphotropic virus type I (HTLV-I) in the pathogenesis of Sjogren's syndrome (SS). Methods. In HTLV-I-seropositive patients with SS, HTLV-I proviral DNA in the labial salivary glands (SG) was detected by polymerase chain reaction (PCR) amplification of the extracted cellular DNA, and the localization in the SG was examined by in situ PCR hybridization. Results. The cellular DNA extracted from the SG contained full HTLV-I proviral DNA, which was present in the nucleus of the infiltrating T cells, but not in either the SG epithelial cells or the acidar cells. Furthermore, the viral loads in the SG were-8 times to 9 X lo3 times higher than those in the peripheral blood mononuclear cells. Conclusion. Accumulation of HTLV-I-infected T cells in the SG suggests that HTLV-I likely causes the self-reactive T cells to proliferate, which, as a result, induces SS. Human T lymphotropic virus type I (HTLV-I) was originally identified as a causative agent of adult T

Role of Viral Infections in the Pathogenesis of Sjögren’s Syndrome: Different Characteristics of Epstein-Barr Virus and HTLV-1

“…With respect to HTLV-1-seropositive patients with SS, an investigation using an in situ PCR technique detected HTLV-1 proviral DNA in infiltrating MNCs but not salivary gland epithelial cells of these patients [121]. In contrast, we detected tax gene in 18% of the salivary glands of HTLV-1-seronegative SS patients by nested PCR [122], suggesting that the involvement of HTLV-1 in HTLV-1-seronegative patients might be limited because the viral load in salivary glands from HTLV-1-seronegative SS patients was much lower than that from HTLV-1-seropositive patients. A study conducted in France and using ISH detected HTLV-1 RNA in both salivary gland epithelial cells and lymphoid cells of HTLV-1-seronegative SS patients, although tax gene was expressed in LSGs from these patients [123].…”

Salivary Glands and Viral Pathogenesis

“…In vitro studies in primary SG epithelial cells cocultured with HTLV-1-infected T cells showed that SG epithelial cells can be infected with HTLV-1, albeit at low rates, and that coincubation with infected cells leads to the production of proinflammatory cytokines (Nakamura et al 2015). Further, HTLV-I-specific T cells are present at high levels in the SGs of infected individuals, suggesting a potential role in SG dysfunction (Ohyama et al 1998).…”

“…Several groups have since detected high levels of HTLV-1 tax in the SGs of patients with SjD (Sumida et al 1994; Mariette et al 2000). The cellular localization of tax is unclear, as some studies found HTLV-1 gene expression in the ductal lumen and inflammatory infiltrate (Tangy et al 1999) while another only found HTLV-1 gene expression in the surrounding lymphocytic cells (Ohyama et al 1998). One group detected HTLV-1 protein p19 in addition to tax in the acinar and ductal cells of the minor SGs (Lee et al 2012).…”

Is Sjögren's syndrome a retroviral disease?

“…The authors found accumulation of HTLV-I-infected T cells expressing TCR with a conserved motif in both HTLV-I-associated and idiopathic SS [18]. In another study among HTLV-I-seropositive patients with SS, HTLV-I proviral DNA in the LSG was detected by polymerase chain reaction (PCR) and the localization of the viral DNA in the LSG was examined by in situ PCR hybridization [19]. The cellular DNA extracted from the LSG contained full HTLV-I proviral DNA, which was present in the nucleus of the infiltrating T cells but not in the epithelial or the acinar cells of the salivary glands.…”