Decreased Dipeptidyl Peptidase IV Enzyme Activity of Plasma Soluble CD26 and Its Inverse Correlation with HIV-1 RNA in HIV-1 Infected Individuals

Hosono, Osamu; Homma, Teiichi; Kobayashi, Hiroshi; Munakata, Yasuhiko; Nojima, Yoshihisa; Iwamoto, Aikichi; Morimoto, Chikao

doi:10.1006/clim.1999.4711

Cited by 25 publications

(21 citation statements)

References 47 publications

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“…Antigen recognition is the preserve of CD4+ T-cells expressing CD26/DPPIV which proliferate in response to soluble antigens and activate MHC-restricted cytotoxic T cells resulting in annihilation of virally infected cells [20,27]. This has been supported by findings that antigen response in HIV-1 infected individuals could be restored by addition of soluble CD26/DPPIV in vitro, suggesting an important role for CD26/DPPIV in HIV-specific immunity [28]. …”

Section: Discussionmentioning

confidence: 99%

CD26/dipeptidyl peptidase IV (CD26/DPPIV) is highly expressed in peripheral blood of HIV-1 exposed uninfected Female sex workers

Songok

Osero

McKinnon

et al. 2010

Virol J

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BackgroundDesign of effective vaccines against the human immunodeficiency virus (HIV-1) continues to present formidable challenges. However, individuals who are exposed HIV-1 but do not get infected may reveal correlates of protection that may inform on effective vaccine design. A preliminary gene expression analysis of HIV resistant female sex workers (HIV-R) suggested a high expression CD26/DPPIV gene. Previous studies have indicated an anti-HIV effect of high CD26/DPPIV expressing cells in vitro. Similarly, high CD26/DPPIV protein levels in vivo have been shown to be a risk factor for type 2 diabetes. We carried out a study to confirm if the high CD26/DPPIV gene expression among the HIV-R were concordant with high blood protein levels and its correlation with clinical type 2 diabetes and other perturbations in the insulin signaling pathway.ResultsA quantitative CD26/DPPIV plasma analysis from 100 HIV-R, 100 HIV infected (HIV +) and 100 HIV negative controls (HIV Neg) showed a significantly elevated CD26/DPPIV concentration among the HIV-R group (mean 1315 ng/ml) than the HIV Neg (910 ng/ml) and HIV + (870 ng/ml, p < 0.001). Similarly a FACs analysis of cell associated DPPIV (CD26) revealed a higher CD26/DPPIV expression on CD4+ T-cells derived from HIV-R than from the HIV+ (90.30% vs 80.90 p = 0.002) and HIV Neg controls (90.30% vs 82.30 p < 0.001) respectively. A further comparison of the mean fluorescent intensity (MFI) of CD26/DPPIV expression showed a higher DPP4 MFI on HIV-R CD4+ T cells (median 118 vs 91 for HIV-Neg, p = 0.0003). An evaluation for hyperglycemia, did not confirm Type 2 diabetes but an impaired fasting glucose condition (5.775 mmol/L). A follow-up quantitative PCR analysis of the insulin signaling pathway genes showed a down expression of NFκB, a central mediator of the immune response and activator of HIV-1 transcription.ConclusionHIV resistant sex workers have a high expression of CD26/DPPIV in tandem with lowered immune activation markers. This may suggest a novel role for CD26/DPPIV in protection against HIV infection in vivo.

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Section: Discussionmentioning

confidence: 99%

CD26/dipeptidyl peptidase IV (CD26/DPPIV) is highly expressed in peripheral blood of HIV-1 exposed uninfected Female sex workers

Songok

Osero

McKinnon

et al. 2010

Virol J

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“…CD26 expression and activity may be reduced in T-cell subsets from patients with active HIV [108,109], but increased in HIV-infected subjects with immune reconstitution [110]. In contrast, serum DPP-IV activity is decreased during pregnancy [111], in subjects with active Crohn's disease [112], major depressive illness [113,114], eating disorders [115], active systemic lupus erythematosis [116] or rheumatoid arthritis [117].…”

Section: Cd26/dpp-iv Activity and Diseasementioning

confidence: 99%

Therapeutic potential of dipeptidyl peptidase IV inhibitors for the treatment of type 2 diabetes

Drucker¹

2003

Expert Opinion on Investigational Drugs

219

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Incretins are peptide hormones, exemplified by glucose-dependent insulinotropic peptide and glucagon-like peptide 1 that are released from the gut in response to nutrient ingestion and enhance glucose-stimulated insulin secretion. Incretin action is terminated due to N-terminal cleavage of the peptides by the aminopeptidase dipeptidyl peptidase IV (DPP-IV). Hence, inhibition of glucose-dependent insulinotropic peptide and glucagon-like peptide 1 degradation via reduction of DPP-IV activity represents an innovative strategy for enhancing incretin action in vivo. This review summarises the biology of incretin action, the structure, expression and pleiotropic biological activities of DPP-IV and provides an overview of the rationale, potential merits and theoretical pitfalls in the development of DPP-IV inhibitors for the treatment of type 2 diabetes.

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“…71 We have shown that the DPPIV enzyme activity of plasma sCD26 was low in HIV-1-infected individuals, and was inversely correlated with HIV-1 RNA, and that the in vitro addition of recombinant sCD26 could enhance purified protein derivative (PPD)-induced lymphocyte proliferation. 72 These results suggest that the specific DPPIV enzyme activity of plasma sCD26 in HIV-1-infected individuals contributes to the immunopathogenesis of HIV infection.…”

Section: Role Of Cd26 In Autoimmune Diseases and Other Immune-mediatementioning

confidence: 82%

CD26: a key molecule in immune regulation and autoimmune diseases

Hosono

Ohnuma

Dang

et al. 2003

Modern Rheumatology

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In this review, we focus on major aspects of the biology of CD26, a dipeptidyl peptidase IV (DPPIV)-containing surface glycoprotein with multiple functions. In particular, we discuss findings demonstrating that CD26/ DPPIV has an essential role in immune regulation as a T cell activation molecule and a regulator of chemokine function. We also review recent studies that identify key cellular molecules that physically associate with CD26 and the potential consequences of their interaction, including those with clinically related implications. Furthermore, we present work suggesting a role for CD26 in the pathophysiology of immune-mediated disorders as well as autoimmune diseases. We present recent studies that investigate the potential role of CD26 as a molecular target for novel treatment modalities for immune-mediated diseases, with work involving the use of anti-CD26 monoclonal antibody, DPPIV inhibitors, and soluble CD26 molecules.

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Decreased Dipeptidyl Peptidase IV Enzyme Activity of Plasma Soluble CD26 and Its Inverse Correlation with HIV-1 RNA in HIV-1 Infected Individuals

Cited by 25 publications

References 47 publications

CD26/dipeptidyl peptidase IV (CD26/DPPIV) is highly expressed in peripheral blood of HIV-1 exposed uninfected Female sex workers

CD26/dipeptidyl peptidase IV (CD26/DPPIV) is highly expressed in peripheral blood of HIV-1 exposed uninfected Female sex workers

Therapeutic potential of dipeptidyl peptidase IV inhibitors for the treatment of type 2 diabetes

CD26: a key molecule in immune regulation and autoimmune diseases

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