T Lymphocytes in Sjögren’s Syndrome: Contributors to and Regulators of Pathophysiology

Abstract

Sjögren's syndrome is a chronic autoimmune disorder characterized by lymphocytic infiltration and malfunction of the exocrine glands, resulting in dry mouth and eyes. This multigenic and multifunctional disease can present as primary Sjögren's syndrome or secondary to an underlying connective tissue disease. Immune activation subsequent to activation or apoptosis of glandular epithelial cells in genetically predisposed individuals may expose autoantigens, which engage self-perpetuating T cell dependent autoimmune sequelae. The cellular and molecular context of this immune response may drive proinflammatory (Th1 and Th17) and restrain inhibitory (Treg) pathways. Inability to suppress the immune response results in persistent tissue damage and compromised function of salivary and lacrimal glands. Defining the contributions of participating T cells may unravel strategies for therapeutic intervention.

Systemic and Local Interleukin-17 and Linked Cytokines Associated with Sjögren’s Syndrome Immunopathogenesis

“…Early periductal infiltration of activated T cells leads to an accumulation of B cells, along with antigen-presenting macrophages and dendritic cells. 2,3 The prevailing paradigm is that salivary gland (SG) lesions in patients with SS are populated with CD4 ϩ T helper type 1 (Th1) lymphocytes and their products, notably interferon-␥ (IFN␥), which orchestrate tissue damage and chronicity. Recently, however, additional Th cell populations have been recognized and linked to autoimmune sequelae, 4 prompting re-evaluation of the cellular constituents of SG lesions.…”

B7‐H4 deficiency in salivary gland of patients with primary Sjögren's syndrome impairs the regulatory effect on T cells

“…The prominent histopathological change is an extensive lymphocytic infiltration in salivary and lachrymal glands, and the majority of infiltrating cells in the salivary glands of SS patients are T cells, predominantly CD4 + T cells. 2,19 Currently, attention of researchers has focused on subsets of CD4 + T cells, including Th1, Th17 cells and Tregs cells, and their function. 2 However, few studies have centred on the interaction between T cell activation and SGECs in pSS.…”

“…2,19 Currently, attention of researchers has focused on subsets of CD4 + T cells, including Th1, Th17 cells and Tregs cells, and their function. 2 However, few studies have centred on the interaction between T cell activation and SGECs in pSS. In fact, as early as 1999, the expression of B7 family costimulatory molecules has been found on SGECs in pSS patients, including B7.1 and B7.2, indicating the activate status of the cells.…”

“…1 The pathogenesis of SS is not fully defined, but is related to the massive lymphocytic infiltration in the exocrine gland that is a hallmark of pSS. 1,2 Because of the widespread involvement of various epithelial cells, pSS has also been described as autoimmune epithelitis. 3,4 Salivary gland epithelial cells (SGEC) are able to present antigens and play an important role as initiators of T cell responses or as targets attacked by T cells in immune salivary gland lesions in pSS.…”

Dry eye disease caused by viral infection: review

“…Once the innate immune response is initiated in glandular and dendritic cells there is an up-regulation of adhesion proteins and an increased production of chemokines that become activated and start acting as antigen-presenting cells. Those events could eventually lead to overproduction of immunoglobulins, autoantibodies and memory lymphocytes and subsequently tissue damage and dysfunction due to apoptosis and inflammation (12) . The occurrence of Sjögren syndrome-like illness, reported as dry eye symptoms or signs, in patients having confirmed viral infections, such as human T-cell lymphotropic virus (HTLV), human immunodeficien cy virus (HIV), Epstein-Barr virus (EBV), and hepatitis C virus (HCV), as well as the beneficial effect of anti-viral treatment, brings circumstantial evi dence that their mechanism maybe pathogenically associated (3,13) .…”