On the role of CD26 in CD4 memory T cells

Cordero, Oscar J.; Chun-ping, Yang; Bell, Eric B.

doi:10.1016/j.imbio.2006.12.002

Cited by 8 publications

(8 citation statements)

References 43 publications

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“…Therefore, sitagliptin is highly unlikely to alter the ADA-binding properties of DPP-IV. However, since the CD26 molecule does not associate with ADA in mice its impact on T-cell function cannot be addressed in rodents [ 43 ]. DPP-IV has also been reported to associate with CD45 and could thereby modulate signal transduction [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

Genetic ablation or pharmacological blockade of dipeptidyl peptidase IV does not impact T cell-dependent immune responses

et al. 2009

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BackgroundCurrent literature suggests that dipeptidyl peptidase IV (DPP-IV; CD26) plays an essential role in T-dependent immune responses, a role that could have important clinical consequences. To rigorously define the role of DPP-IV in the immune system, we evaluated genetic and pharmacological inhibition of the enzyme on T-dependent immune responses in vivo.ResultsThe DPP-IV null animals mounted robust primary and secondary antibody responses to the T dependent antigens, 4-hydroxy-3-nitrophenylacetyl-ovalbumin (NP-Ova) and 4-hydroxy-3-nitrophenylacetyl-chicken gamma globulin (NP-CGG), which were comparable to wild type mice. Serum levels of antigen specific IgM, IgG1, IgG2a, IgG2b and IgG3 were similar between the two groups of animals. DPP-IV null animals mounted an efficient germinal center reaction by day 10 after antigen stimulation that was comparable to wild type mice. Moreover, the antibodies produced by DPP-IV null animals after repeated antigenic challenge were affinity matured. Similar observations were made using wild type animals treated with a highly selective DPP-IV inhibitor during the entire course of the experiments. T cell recall responses to ovalbumin and MOG peptide, evaluated by measuring proliferation and IL-2 release from cells isolated from draining lymph nodes, were equivalent in DPP-IV null and wild type animals. Furthermore, mice treated with DPP-IV inhibitor had intact T-cell recall responses to MOG peptide. In addition, female DPP-IV null and wild type mice treated with DPP-IV inhibitor exhibited normal and robust in vivo cytotoxic T cell responses after challenge with cells expressing the male H-Y minor histocompatibility antigen.ConclusionThese data indicate Selective inhibition of DPP-IV does not impair T dependent immune responses to antigenic challenge.

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Section: Discussionmentioning

confidence: 99%

Genetic ablation or pharmacological blockade of dipeptidyl peptidase IV does not impact T cell-dependent immune responses

et al. 2009

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“…It is down-regulated on cells that undergo apoptosis and upregulated on maturing thymocytes, reaching the highest level of CD26/DPP4 expression in mature CD4 or CD8 single-positive T cells within the thymus [94][95][96]. Findings are conflicted in the periphery, but describe the expression of CD26/DPP4 favourably as a characteristic of memory T cells, with CD26/DPP4 bright cells responding maximally to recall antigens [97][98][99][100]. CD26/DPP4 has shown the ability to act as a non-integrin receptor, being able to bind fibronectin and collagen [101,102].…”

Section: T Cell Developmentmentioning

confidence: 99%

Cut to the chase: a review of CD26/dipeptidyl peptidase-4's (DPP4) entanglement in the immune system

Klemann

Wagner

Stephan

et al. 2016

Clinical and Experimental Immunology

373

437

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SummaryCD26/DPP4 (dipeptidyl peptidase 4/DP4/DPPIV) is a surface T cell activation antigen and has been shown to have DPP4 enzymatic activity, cleaving-off amino-terminal dipeptides with either L-proline or L-alanine at the penultimate position. It plays a major role in glucose metabolism by Nterminal truncation and inactivation of the incretins glucagon-like peptide-1 (GLP) and gastric inhibitory protein (GIP). In 2006, DPP4 inhibitors have been introduced to clinics and have been demonstrated to efficiently enhance the endogenous insulin secretion via prolongation of the half-life of GLP-1 and GIP in patients. However, a large number of studies demonstrate clearly that CD26/DPP4 also plays an integral role in the immune system, particularly in T cell activation. Therefore, inhibition of DPP4 might represent a double-edged sword. Apart from the metabolic benefit, the associated immunological effects of long term DPP4 inhibition on regulatory processes such as T cell homeostasis, maturation and activation are not understood fully at this stage. The current data point to an important role for CD26/DPP4 in maintaining lymphocyte composition and function, T cell activation and co-stimulation, memory T cell generation and thymic emigration patterns during immune-senescence. In rodents, critical immune changes occur at baseline levels as well as after in-vitro and in-vivo challenge. In patients receiving DPP4 inhibitors, evidence of immunological side effects also became apparent. The scope of this review is to recapitulate the role of CD26/DPP4 in the immune system regarding its pharmacological inhibition and T cell-dependent immune regulation.Keywords: autoimmunity, B cell, cell activation, chemokines, T cells Structure and characterization of CD26Originally described 50 years ago [1], the lymphocyte cell surface protein CD26 possess a dipeptidyl peptidase-4 (DPP4) activity. It cleaves dipeptides from the N-termini of oligopeptides and smaller peptides with proline or alanine at the penultimate position, as illustrated in Fig. 1b [International Union of Biochemistry and Molecular Biology (IUBMB) Enzyme Nomenclature EC 3.4.14.5].CD26/DPP4 is a homodimer and an integral type II glycoprotein anchored to the membrane by its signal peptide. The primary structure consists of a short six amino acid cytoplasmic tail, a 22 amino acid transmembrane, a 738 amino acid extracellular portion comprised of a flexible stalk, glycosylation-rich region, cysteine-rich region and catalytic region with the catalytic triad Ser 630 , Asp 708 and His 740 (Fig. 1e). Recent studies have revealed that the transmembrane region contributes to enzyme activity and quaternary structure by dimerization [2]. The crystal structure of human CD26/DPP4 has been elucidated to reveal two domains: an eight-bladed propeller and an a/b-hydrolase domain. The propeller is open and consists of two subdomains made up of blades II-V and VI-VIII for the glycosylation-rich and cysteine-rich regions, respectively (Fig. 1d). Most monoclonal anti-CD26/DPP4 antibodies,...

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“…In this capacity DPIV is referred to as CD26, and is expressed on T‐, B‐, and natural killer cells 7. CD26 has a costimulatory role in T‐cell activation and numerous signal transduction pathways via interactions with the chemokine receptor CXCR4, as well as adenosine deaminase (ADA) and CD45 8–10. The involvement of CD26 in T‐cell regulatory functions and its role in colitis is less well studied 11–13…”

mentioning

confidence: 99%

Dipeptidyl peptidase expression during experimental colitis in mice

Yazbeck

Sulda

Howarth

et al. 2010

Inflammatory Bowel Diseases

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DP expression and activity are differentially regulated during DSS colitis, suggesting a pathophysiological role for these enzymes in human inflammatory bowel disease (IBD). DP inhibitors impaired neutrophil recruitment and maintenance of the Treg population during DSS-colitis, providing further preclinical evidence for the potential therapeutic use of these inhibitors in IBD. Finally, DPIV appears to play a critical role in mediating the protective effect of DP inhibitors.

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On the role of CD26 in CD4 memory T cells

Cited by 8 publications

References 43 publications

Genetic ablation or pharmacological blockade of dipeptidyl peptidase IV does not impact T cell-dependent immune responses

Genetic ablation or pharmacological blockade of dipeptidyl peptidase IV does not impact T cell-dependent immune responses

Cut to the chase: a review of CD26/dipeptidyl peptidase-4's (DPP4) entanglement in the immune system

Dipeptidyl peptidase expression during experimental colitis in mice

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