Antigen-presenting effects of effector memory Vγ9Vδ2 T cells in rheumatoid arthritis

Abstract

Rheumatoid arthritis is an autoimmune disease that primarily affects the limbs, but the pathogenic mechanism remains unclear. cd T cells, a T-cell subpopulation, are characterized by multiple biological functions and associated with a variety of diseases. This study investigated the antigen-presenting effects of cd T cells and their relationship with rheumatoid arthritis development. We found that Vc9Vd2 T cells (the predominant subtype of cd T cells in peripheral blood) were activated by isopentenyl pyrophosphate to continuously proliferate and differentiate into effector memory cells. The effector memory Vc9Vd2 T cells exhibited phenotypic characteristics of specific antigen-presenting cells, including high HLA-DR and CD80/86 expression. These Vc9Vd2 T cells could present soluble antigens and synthetic peptides to CD41 T cells. Vc9Vd2 T cells with different phenotypes showed different cytokine secretion patterns. Effector memory Vc9Vd2 T cells simultaneously secreted not only interferon (IFN)-c but also IL-17. The peripheral blood and joint synovial fluid from RA patients contained numerous heterogeneous cd T cells that were predominantly effector memory Vc9Vd2 T cells with the ability to secrete inflammatory factors. We also found that cd T cells had a similar antigen-presenting capability to B cells. These results suggest that during the development of rheumatoid arthritis, cd T cells can aggravate immune dysfunction and produce abnormal immune damage by secreting cytokines and inducing inflammatory cells to participate in synergistic inflammatory responses. Furthermore, cd T cells can behave similarly to B cells to present viral peptides and autoantigen peptides to CD4 1 T cells, thus sustaining CD4 1 T-cell activation.

Reduction of CD18 Promotes Expansion of Inflammatory γδ T Cells Collaborating with CD4+ T Cells in Chronic Murine Psoriasiform Dermatitis

“…Using (57,58), arthritis (59)(60)(61)(62), and inflammatory bowel disease (63), stimulating functions of gd T cells on CD4 + T cells and inflammation have been reported. gd T cells functioned as APCs, enhancing CD4 + T cell activation (55,56), or promoted differentiation of naive T cells into autoreactive Th17 cells while inhibiting peripheral Tregs (57,58).…”

Human Vγ9/Vδ2 T cells: Innate adaptors of the immune system

“…As such, these 'Vc9/Vd2 TAPCs' are capable of inducing MHC class II restricted CD4 + T cell responses upon presentation of the staphylococcal superantigen toxic shock syndrome toxin 1 (TSST-1) that crosslinks HLA-DR on the APC surface with the TCR of responder cells carrying a Vb2 chain, and in mixed lymphocyte responses as a reaction to donor mismatched MHC class II alleles [116]. Moreover, Vc9/Vd2 T-APCs have also been shown to induce antigen-specific CD4 + T cell responses upon direct presentation of antigenic peptides or upon uptake and intracellular processing of microbial antigens like M. tuberculosis PPD and tetanus toxoid [116,123].…”

“…Indirect support for a possible role as APC stems from observations that HLA-DR is expressed by activated Vc9/Vd2 T cells in patients with severe inflammation or during acute infection [123,[138][139][140], and in patients receiving intravenous zoledronate with and without 141,142]. However, functional evidence into the potential of activated Vc9/Vd2 T cells to act as APC ex vivo is only beginning to emerge [123,143]. NKT cells are a heterogeneous group of T cells that share properties of both T cells and NK cells [144][145][146].…”

“…As such, these 'Vc9/Vd2 TAPCs' are capable of inducing MHC class II restricted CD4 + T cell responses upon presentation of the staphylococcal superantigen toxic shock syndrome toxin 1 (TSST-1) that crosslinks HLA-DR on the APC surface with the TCR of responder cells carrying a Vb2 chain, and in mixed lymphocyte responses as a reaction to donor mismatched MHC class II alleles [116]. Moreover, Vc9/Vd2 T-APCs have also been shown to induce antigen-specific CD4 + T cell responses upon direct presentation of antigenic peptides or upon uptake and intracellular processing of microbial antigens like M. tuberculosis PPD and tetanus toxoid [116,123].With regard to the functional outcome of Vc9/Vd2 T-APC driven CD4 + T cell responses, the abundant expression of pro-inflammatory cytokine such as IFN-c and TNF-a by activated Vc9/Vd2 T cells may mainly induce a polarization of CD4 + T cells toward a Th1 phenotype, although at low APC ratios an expression of IL-4 by CD4 + T cells was observed [116]. Depending on the culture conditions, Vc9/Vd2 T cells clearly assume different functions including distinct cytokine profiles [49,74,72,[124][125][126], and hence more research is needed to delineate whether Vc9/Vd2 T-APCs may induce different 'flavors' of CD4 + T cell responses (Th1, Th2, Th17, Th22, Treg), and what the signals involved in such a polarization are.…”

Natural killer cell and gamma delta T cell alterations in enthesitis related arthritis category of juvenile idiopathic arthritis

“…In oligoarticular JIA a specific subset of γδ-T cells (Vδ1+Vγ9+) was associated with milder disease but they did not study the total γδ-T cells or IL-17 production by them [35]. Recent study on RA has revealed that the PB and SF γδ-T cells, on stimulation with isopentenyl pyrophosphate (IPP) secrete more IL-17 [36]. Hence in ERA γδ-T cells may act as a source of IL-17 and perpetuate inflammation.…”