CD8+ T Lymphocytes: Crucial Players in Sjögren's Syndrome

Abstract

Primary Sjögren's syndrome (pSS) is a chronic autoimmune disease associated with damage to multiple organs and glands. The most common clinical manifestations are dry eyes, dry mouth, and enlarged salivary glands. Currently, CD4⁺ T lymphocytes are considered to be key factors in the immunopathogenesis of pSS, but various studies have shown that CD8⁺ T lymphocytes contribute to acinar injury in the exocrine glands. Therefore, in this review, we discussed the classification and features of CD8⁺ T lymphocytes, specifically describing the role of CD8⁺ T lymphocytes in disease pathophysiology. Furthermore, we presented treatment strategies targeting CD8⁺ T cells to capitalize on the pathogenic and regulatory potential of CD8⁺ T lymphocytes in SS to provide promising new strategies for this inflammatory disease.

Keywords: CD8+ T lymphocyte; Sjögren’s syndrome; immune regulation; pathophysiology; tissue resident lymphocyte.

Figure 1

Activated CD8⁺T cells are involved in the mechanism of salivary gland injury. The upper part of the panel shows naïve CD8⁺ T differentiated into subgroups. CTLs and memory CD8⁺ T cells play important roles in the organization. The lower part of the panel highlights the tissues damage caused by activated CD8⁺ T entering the salivary glands. Pathological examination of apoptotic acinar cells in the salivary glands and lacrimal glands of patients with SS revealed the accumulation of CD8⁺ T cells and fewer CD4⁺ T cells expressing integrin αEβ7 (CD103) (12). A kind of cytotoxic memory T cell called CD8⁺ T_RM cells and CTLs producing GrB/perforin can induce acinar cells death (53, 72). CTLs recognize pMHCI presented by the acinar cells, then specific T cell receptor (TCR) and co-receptors to contact parts, promoting the secretion of such as IFN-γ, TNF-α, GrB/perforin. In addition, CTLs can express FasL or secrete TNF-α, which bind to Fas and TNF receptors (TNFR) on the surface of acinar cells respectively and induce apoptosis mediated by caspase signaling pathways (73, 74). There are also a large number of inflammatory cells such as CD4⁺T cells and B cells in the glandular tissue, which cooperate with CD8⁺T cells to play an immune effect and cause tissues damage. Treg *: CXCR5⁺Foxp3^+/−CD8⁺Treg; Tfc *: CXCR5⁺PD-1^int-CD8⁺Tfc; Tfh *: CXCR5⁺PD-1^highCD8⁺Tfh.