The Role of Gamma Delta T Cells in Autoimmune Rheumatic Diseases

Abstract

Autoimmune rheumatic diseases (ARDs), affecting ~1–1.5% of all humans, are associated with considerable life long morbidity and early mortality. Early studies in the 1990s showed numerical changes of the recently discovered γδ T cells in the peripheral blood and in affected tissues of patients with a variety of ARDs, kindling interest in their role in the immuno-pathogenesis of these chronic inflammatory conditions. Indeed, later studies applied rapid developments in the understanding of γδ T cell biology, including antigens recognized by γδ T cells, their developmental programs, states of activation, and cytokine production profiles, to analyze their contribution to the pathological immune response in these disorders. Here we review the published studies addressing the role of γδ T in the major autoimmune rheumatic diseases, including rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, systemic lupus erythematosus and scleroderma, and animal models thereof. Due to their unique properties spanning adaptive and innate immune functions, the ever deeper understanding of this unique T cell population is shedding new light on the pathogenesis of, while potentially enabling new therapeutic approaches to, these diseases.

Epstein-Barr Virus and Systemic Autoimmune Diseases

“…These diseases share several genetic and environmental factors, in particular the predisposing effect of certain HLA-DRB1 alleles (although not exactly identical alleles), the predisposing effect of EBV infection and of factors, which can be related to EBV infection (e.g. vitD deficiency) (Table 2) (106,107,(160)(161)(162)(163)(164)(165)(166)(167)(168)(169)(170)(171).…”

BTN2A1, an immune checkpoint targeting Vγ9Vδ2 T cell cytotoxicity against malignant cells

“…Herein, we have discussed the use of inhibiting BTN2A1 antibodies in an oncology setting as tools to understand the role of BTN2A1 in the Vg9Vd2 T cell anti-tumor response. For therapeutic applications, it would be interesting to investigate these inhibitory BTN2A1 antibodies in an autoimmune setting, since Vg9Vd2 T cells have been reported to be dysregulated is several autoimmune diseases (Bank, 2020).…”

SLAM Associated Protein Signaling in T Cells: Tilting the Balance Toward Autoimmunity

“…Finally, while our review is focused on T cell -B cell signaling, the SLAM receptors are expressed on most hematopoietic cells, including early progenitor cells, myeloid cells, and lymphoid cells, and all these likely contribute to the overall immune response. In the thymus, the SLAM/SAP signaling pathway is critical for the development of unconventional, non-MHC restricted, IL-17 and IFN-g producing gd T cells that likely play a unique and important role in autoimmunity (82,83). In phagocytic myeloid cells, the SLAM receptors contribute to microbial pathogen recognition and regulation of cell trafficking and microbicidal activity in the inflammatory state (84).…”