CD26/DPPIV Signal Transduction Function, but Not Proteolytic Activity, Is Directly Related to Its Expression Level on Human Th1 and Th2 Cell Lines as Detected with Living Cell Cytochemistry

Boonacker, Emil; Wierenga, Eddy A.; Smits, Hermelijn H.; Noorden, C. J. F. Van

doi:10.1177/002215540205000903

Cited by 61 publications

(49 citation statements)

References 34 publications

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“…CD26 has a known function as an activation marker for T cells, B cells, NK cells, and macrophages but has also been cited as a maturation marker for T lymphocytes (4). Upon stimulation of Th1 and Th2 cell lines, it was demonstrated that CD26 expression was 3-to 6-fold higher on Th1 cells, which further correlated with higher intracellular IFN-␥ levels (4).…”

Section: Discussionmentioning

confidence: 99%

Early Immune Markers Associated withMycobacterium aviumsubsp.paratuberculosisInfection in a Neonatal Calf Model

Stabel

Robbe‐Austerman

2011

Clin Vaccine Immunol

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The objective of this study was to observe early markers of cell-mediated immunity in naïve calves infected with Mycobacterium avium subsp. paratuberculosis and how expression of these markers evolved over the 12-month period of infection. Groups for experimental infection included control (noninfected), oral (infected orally with M. avium subsp. paratuberculosis strain K-10), oral/DXM (pretreatment with dexamethasone before oral inoculation), intraperitoneal (i.p.) inoculation, and oral/M (oral inoculation with mucosal scrapings from a cow with clinical disease) groups. One of the earliest markers to emerge was antigen-specific gamma interferon (IFN-␥). Only i.p. inoculated calves had detectable antigen-specific IFN-␥ responses at 7 days, with responses of the other infection groups becoming detectable at 90 and 120 days. All infection groups maintained robust IFN-␥ responses for the remainder of the study. At 1 month, calves in the oral and oral/M groups had higher antigen-stimulated interleukin-10 (IL-10) levels than calves in the other treatment groups, but IL-10 secretion declined by 12 months for all calves. T-cell activation markers such as CD25, CD26, CD45RO, and CD5 were significantly upregulated in infected calves compared to noninfected controls. Oral inoculation of calves resulted in significantly increased antigen-specific lymphocyte proliferation at 9 and 12 months, as well as inducible nitric oxide synthase (iNOS) secretion at 6 and 12 months. These results demonstrate that infection of naïve calves with M. avium subsp. paratuberculosis invoked early immunologic responses characterized by robust antigen-specific IFN-␥ responses and induction of CD25 and CD45RO expression on T-cell subsets. These were followed by antigen-specific lymphocyte proliferation, iNOS secretion, and expression of CD26 and CD5 bright markers in the latter part of the 12-month study.Deciphering host immune responses upon exposure to Mycobacterium avium subsp. paratuberculosis, differentiating the responses due to exposure from true infection, and then further characterizing responses at different stages of infection have been daunting and complex tasks that remain elusive. Early measures of host immune responses to infection with mycobacteria, including M. avium subsp. paratuberculosis, have been dominated by a strong bias toward Th1-mediated gamma interferon (IFN-␥) production. Higher levels of antigen-specific IFN-␥ secreted by peripheral blood mononuclear cells (PBMCs) have been reported for animals in the early stages of M. avium subsp. paratuberculosis infection, whether it be natural or experimental infection (11,18,22,24). Since IFN-␥ is a key effector cytokine involved in the activation of T cells and macrophages, maturation of dendritic cells, upregulation of major histocompatibility complex (MHC) class I and II molecules, and production of reactive oxygen and nitrogen species by macrophages, it is purported to be not only an immune response variable but also a correlate of immune protection (7,16). However, it is u...

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Section: Discussionmentioning

confidence: 99%

Early Immune Markers Associated withMycobacterium aviumsubsp.paratuberculosisInfection in a Neonatal Calf Model

Stabel

Robbe‐Austerman

2011

Clin Vaccine Immunol

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“…Expression of the "novel" Th2-associated genes in these clusters has not been reported previously in the context of specific allergentriggered T cell memory responses in atopics. Some have been observed previously in experiments broadly related to Th2 immunity, notably 1) CISH was induced by IL-4 in mouse T cells (21) and was also detected in human Th2 cells (55); 2) IL-17RB was reported to be anti-CD3/CD28 up-regulated in restimulated Ryespecific T cells (14) and in Th2 cell lines (19); 3) MAL was reported in a differential display screen of resting peripheral blood T cells from atopics with dermatitis and asthma, but follow-up PCR experiments failed to confirm these observations (56); 4) DPP4 was detected in bronchial biopsies of allergic asthmatics (57) and in Th1 and Th2 cells (58). To our knowledge, this is the first report of any associations of DACT1, NDFIP2, GNG8, NSMCE1, and RAB27B with atopy or Th2 responses.…”

Section: Study Design and Statistical Analysesmentioning

confidence: 99%

Identification of Novel Th2-Associated Genes in T Memory Responses to Allergens

Bosco

McKenna

Devitt

et al. 2006

The Journal of Immunology

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Atopic diseases are associated with hyperexpression of Th2 cytokines by allergen-specific T memory cells. However, clinical trials with recently developed Th2 inhibitors in atopics have proven disappointing, suggesting underlying complexities in atopy pathogenesis which are not satisfactorily explained via the classical Th1/Th2 paradigm. One likely possibility is that additional Th2-associated genes which are central to disease pathogenesis remain unidentified. The aim of the present study was to identify such novel Th2-associated genes in recall responses to the inhalant allergen house dust mite. In contrast to earlier human microarray studies in atopy which focused on mitogen-activated T cell lines and clones, we concentrated on PBMC-derived primary T cells stimulated under more physiological conditions of low dose allergen exposure. We screened initially for allergen-induced gene activation by microarray, and validated novel genes in independent panels of subjects by quantitative RT-PCR. Kinetic analysis of allergen responses in PBMC revealed an early wave of novel atopy-associated genes involved in signaling which were coexpressed with IL-4 and IL-4R, followed by a later wave of genes encoding the classical Th2 effector cytokines. We further demonstrate that these novel activation-associated Th2 genes up-regulate in response to another atopy-associated physiological stimulus bacterial superantigen, but remain quiescent in nonphysiological responses in primary T cells or cell lines driven by potent mitogens, which may account for their failure to be detected in earlier microarray studies.

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“…DPPIV -rats display normal immunity [31], yet DPPIV is also a lymphocyte surface protein designated CD26 (GenBank #AAH22183), and mutated CD26 might alter T-cell function [32,33]. Thus, 3(8)21-EGFP or STO xenografts might be tolerated by DPPIV -rats but rejected in wild-type recipients.…”

Section: Mouse Sto Cell Lines Can Be Xenotransplanted Into Nonimmunosmentioning

confidence: 99%

Embryonic Mouse STO Cell–Derived Xenografts Express Hepatocytic Functions in the Livers of Nonimmunosuppressed Adult Rats

et al. 2005

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Cells derived from embryonic mouse STO cell lines differentiate into hepatocytes when transplanted into the livers of nonimmunosuppressed dipeptidylpeptidase IV (DPPIV)-negative F344 rats. Within 1 day after intrasplenic injection, donor cells moved rapidly into the liver and were found in intravascular and perivascular sites; by 1 month, they were intrasinusoidal and also integrated into hepatic plates with approximately 2% efficiency and formed conjoint bile canaliculi. Neither donor cell proliferation nor host inflammatory responses were observed during this time. Detection of intrahepatic mouse COX1 mitochondrial DNA and mouse albumin mRNA in recipient rats indicated survival and differentiation of donor cells for at least 3 months. Mouse COX1 targets were also detected intrahepatically 4-9 weeks after STO cell injection into nonimmunosuppressed wild-type rats. In contrast to STO-transplanted rats, mouse DNA or RNA was not detectable in untreated or mock-transplanted rats or in rats injected with donor cell DNA. In cultured STO donor cells, DPPIV and glucose-6-phosphatase activities were observed in small clusters; in contrast, mouse major histocompatibility complex class I H-2Kq , H-2D q , and H-2L q and class II I-A q markers were undetectable in vitro before or after interferon gamma treatment. Together with H-2K allele typing, which confirmed the Swiss mouse origin of the donor cells, these observations indicate that mouse-derived STO cell lines can differentiate along hepatocytic lineage and engraft into rat liver across major histocompatibility barriers.

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CD26/DPPIV Signal Transduction Function, but Not Proteolytic Activity, Is Directly Related to Its Expression Level on Human Th1 and Th2 Cell Lines as Detected with Living Cell Cytochemistry

Cited by 61 publications

References 34 publications

Early Immune Markers Associated withMycobacterium aviumsubsp.paratuberculosisInfection in a Neonatal Calf Model

Early Immune Markers Associated withMycobacterium aviumsubsp.paratuberculosisInfection in a Neonatal Calf Model

Identification of Novel Th2-Associated Genes in T Memory Responses to Allergens

Embryonic Mouse STO Cell–Derived Xenografts Express Hepatocytic Functions in the Livers of Nonimmunosuppressed Adult Rats

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