CD26 Surface Molecule Involvement in T Cell Activation and Lymphokine Synthesis in Rheumatoid and Other Inflammatory Synovitis

doi:10.1006/clin.1996.0091

Clinical Immunology and Immunopathology

Volume 80, Issue 1, July 1996, Pages 31-37

Clinical Immunology ...

https://doi.org/10.1006/clin.1996.0091 Get rights and content

Abstract

T cell surface expression and the functional role of CD26 antigen (Ag), a surface ectoenzyme involved in T cell activation and migration across the extracellular matrix, were analyzed in the peripheral blood (PB) and synovial fluid (SF) from patients with inflammatory arthritides. CD26 membrane expression on T cells was detected by cytofluorometry using two different monoclonal antibodies, anti-Ta1 and anti-1F7, while cell proliferation and both IL-2 and IFN-γ production were evaluated in anti-CD3- or anti-CD2-stimulated cell cultures after Ag surface modulation with anti-1F7. The results showed that Ta1 and 1F7 Ag expression were increased on T cells from PB of patients with active, but not inactive, rheumatoid arthritis (RA). Most SF T cells from RA or other inflammatory arthritides displayed the memory marker CD45R0 and the Ta1 Ag, but lacked the 1F7 molecule. In addition,in vitro1F7 modulation, which enhanced RA PB T cell proliferation and both IL-2 and IFN-γ synthesis, did not synergize with anti-CD3 or anti-CD2 in inducing IL-2-dependent activation of SF T cells, but reduced IFN-γ production. A spontaneous reappearance of 1F7 Ag on the SF T cell surface was seen after 2–5 days in culture. Phorbol myristate acetate, able to accelerate its reexpression, also restored a normal response of SF T cells to anti-1F7 comitogenic effects. These data confirm a role of the CD26 surface molecule in regulating T cell activation and lymphokine synthesis. This observation may have important implications in the regulation of T cell activity at the joint level during chronic inflammatory processes.

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Cited by (46)

CD26 in autoimmune diseases: The other side of “moonlight protein”
2019, International Immunopharmacology
Citation Excerpt :
Nathalie Busso et al. found that plasma CD26 activity decreases in murine antigen-induced arthritis, which probably influents the regulation of stromal cell-derived factor-1(SDF-1)/SDF-1 receptor (CXCR4) axis [25]. Rats resistant to collagen-induced arthritis are characterized by increased CD26 activity in plasma, on the other hand, decreased CD26 activity in membrane-bound fractions of PBMCs prone to develop arthritis [26]. Regulation of CD26 activity is considered to affect signal transduction, chemokines, proliferation and recruitment of immune cells [27], which suggests that decreased CD26 activity might involve in the pathogenesis of RA [26].
Dipeptidyl peptidase 4 (DPP-4) is a serine protease, which has enzymatic activity to selectively clean the N-terminal dipeptide of peptides and proteins with proline or alanine in the second position. DPP-4 inhibitor has been widely used for the treatment of type 2 diabetes by increasing the level of the glucagon-like peptide-1 and decreasing the glucose level. DPP-4, also known as lymphocyte cell surface protein CD26, plays a core role of T cell immunity. Many roles of CD26 in other immune cells have been found. As a “moonlight protein”, the effect of CD26 in autoimmune diseases has attracted more and more attention. The paper reviewed the function and potential effect of CD26 in autoimmune diseases, which shows CD26 may be a new target of autoimmune diseases deserved further study.
Chemokine isoforms and processing in inflammation and immunity
2017, Journal of Autoimmunity
The first dimension of chemokine heterogeneity is reflected by their discovery and purification as natural proteins. Each of those chemokines attracted a specific inflammatory leukocyte type. With the introduction of genomic technologies, a second wave of chemokine heterogeneity was established by the discovery of putative chemokine-like sequences and by demonstrating chemotactic activity of the gene products in physiological leukocyte homing. In the postgenomic era, the third dimension of chemokine heterogeneity is the description of posttranslational modifications on most chemokines. Proteolysis of chemokines, for instance by dipeptidyl peptidase IV (DPP IV/CD26) and by matrix metalloproteinases (MMPs) is already well established as a biological control mechanism to activate, potentiate, dampen or abrogate chemokine activities. Other posttranslational modifications are less known. Theoretical N-linked and O-linked attachment sites for chemokine glycosylation were searched with bio-informatic tools and it was found that most chemokines are not glycosylated. These findings are corroborated with a low number of experimental studies demonstrating N- or O-glycosylation of natural chemokine ligands. Because attached oligosaccharides protect proteins against proteolytic degradation, their absence may explain the fast turnover of chemokines in the protease-rich environments of infection and inflammation. All chemokines interact with G protein-coupled receptors (GPCRs) and glycosaminoglycans (GAGs). Whether lectin-like GAG-binding induces cellular signaling is not clear, but these interactions are important for leukocyte migration and have already been exploited to reduce inflammation. In addition to selective proteolysis, citrullination and nitration/nitrosylation are being added as biologically relevant modifications contributing to functional chemokine heterogeneity. Resulting chemokine isoforms with reduced affinity for GPCRs reduce leukocyte migration in various models of inflammation. Here, these third dimension modifications are compared, with reflections on the biological and pathological contexts in which these posttranslational modifications take place and contribute to the repertoire of chemokine functions and with an emphasis on autoimmune diseases.
Regulation and roles of CD26/DPPIV in hematopoiesis and diseases
2017, Biomedicine and Pharmacotherapy
Dipeptidyl peptidase IV (DPPIV),¹ on the surface of certain cells, where it is also referred to as CD26, is involved in a vast majority of biological and pathological processes. CD26/DPPIV function contributes to cancer and tumor metastasis as well as inhibition of its expression which alters the expression of immune response-related genes. CD26/DPPIV is a widely distributed multifunctional integral membrane and secreted protein that is defined as early predictive biomarker in HIV, cancer and autoimmunity diseases like diabetes and multiple sclerosis. CD26/DPPIV-chemokine interaction may have a functional role in T-cells and overall immune function. It is expressed at low density on resting T cells, but is upregulated with T cell activation. In this review, we summarize valuable information about detailed biological aspects and pharmacokinetic characteristics of CD26/DPPIV and its clinical efficacy, focusing particularly on the role of CD26/DPPIV in immunological and non-immunological diseases. We also describe our recent work about umbilical cord blood (UCB)² hematopoietic stem cell transplantation strategies in which identified CD26+ cells can be differentiated to immune cells under certain culture condition.
Dipeptidyl peptidase in autoimmune pathophysiology
2011, Advances in Clinical Chemistry
Citation Excerpt :
These findings suggest that these cytokines and CD26 are associated with the inflammation and immune activity in RA. However, expression of CD26/DPPIV on CD3+ T cells in synovial fluid of RA patients has been reported to be decreased, compared to that of healthy adult patients with osteoarthritis [19,118,121]. We reported the presence of CD26+ T cells infiltrating the rheumatoid synovium as demonstrated by immunohistochemical studies, and noted high expression of caveolin-1 in the rheumatoid synovium vasculature and synoviocytes [158].
Dipeptidyl peptidase-IV in synovial fluid and in synovial fluid mononuclear cells of patients with rheumatoid arthritis
2010, Clinica Chimica Acta
Dipeptidyl peptidase-IV (DPP-IV) enzymatic activity controls biological halftime of multiple local mediators. Its deregulation is associated with pathogenesis of several autoimmune diseases, including rheumatoid arthritis (RA). Although DPP-IV is the canonical representative of the group, a number of other proteins have been shown to have similar enzymatic activity. This study was aimed to identify the molecular source of DPP-IV activity in synovial fluid (SF) and fluid mononuclear cells (FMNC) in patients with RA and osteoarthritis (OA). In addition, the association of DPP-IV and the concentration of stromal cell-derived factor-1α (SDF), DPP-IV substrate, were evaluated.
DPP-IV activity was measured by the kinetic fluorimetric method. The expression of studied molecules in FMNC and their concentrations in SF were assayed using flow cytometry and ELISA respectively.
DPP-IV activity in SF, dominantly derived from the canonical DPP-IV, does not significantly differ between RA and OA. However, a significantly lower DPP-IV activity and expression in FMNC was found in RA as opposed to OA patients. Negative correlation between SDF concentration in SF and the relative amount of CD3+CD26+ cells was observed.
We report decreased presence of DPP-IV/CD26 in CD3+ FMNC in RA, which also may participate on impaired balance of SDF concentration in SF.
Modulation of cytokine production and silica-induced lung fibrosis by inhibitors of aminopeptidase N and of dipeptidyl peptidase-IV-related proteases
2009, Life Sciences
Dipeptidyl peptidase IV (DP IV)-related proteases and aminopeptidase N (APN) are drug targets in various diseases. Here we investigated for the first time the effects of DP-IV-related protease inhibitors and APN inhibitors on chronic inflammatory lung diseases.
A murine model of silica (SiO₂)-induced lung fibrosis and in vitro cultures of human lung epithelial cells and monocytes have been used and the influence of silica-treatment and inhibitors on inflammation and fibrosis has been measured.
We found increased inflammation and secretion of the chemokines IL-6, MCP-1 and MIP-α 2 weeks after SiO₂ application, and increased lung fibrosis after 3 months. Treatment with the APN inhibitor actinonin reduced chemokine secretion in the lung and bronchoalveolar lavage fluid, and in cell culture, and decreased the level of fibrosis after 3 months. Treatment with inhibitors of DP-IV-related proteases, or a combination of DP IV inhibitors and APN inhibitors, had no significant effect. We found no obvious side effects of long-term treatment with inhibitors of APN and DP IV.
Overall, our findings show that actinonin, an inhibitor of aminopeptidase N, might modulate chemokine secretion in the lung and thus attenuate the development of lung fibrosis. Additional targeting of DP-IV-related proteases had no significant effect on these processes.

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Regular ArticleCD26 Surface Molecule Involvement in T Cell Activation and Lymphokine Synthesis in Rheumatoid and Other Inflammatory Synovitis

Abstract

Regular Article
CD26 Surface Molecule Involvement in T Cell Activation and Lymphokine Synthesis in Rheumatoid and Other Inflammatory Synovitis