Cell surface characterization of T lymphocytes and allergen-specific T cell clones: Correlation of CD26 expression with T H1 subsets

Willheim, Martin; Ebner, Christof; Baier, Karin; Kern, Wolfgang; Schrattbauer, Karl; Thien, Ralf; Breiteneder, Heimo; Reinisch, Walter; Scheiner, Otto

doi:10.1016/s0091-6749(97)70248-3

Cited by 116 publications

(111 citation statements)

References 36 publications

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“…We studied simultaneously expression of the protein and activity of the proteolytic enzyme in the two different types of polarized Th cells that are involved in cellular (Th1) and humoral (Th2) immune responses and are known to express different levels of CD26 (Willheim et al 1997). We found that the proteolytic activity of CD26/DPPIV is kept at a steady functional level despite a three-to six-fold difference in CD26 expression.…”

Section: Discussionmentioning

confidence: 99%

“…On day 3 of restimulation, CD26 expression and DPPIV activity were measured when differences in CD26/DPPIV expression between Th1 and Th2 cells are most profound (Kähne et al 1996;Willheim et al 1997) …”

Section: Polarization Studiesmentioning

confidence: 99%

“…However, chronic activation of Th1 or Th2 effector cells may lead to autoimmune disorders or allergy, respectively (Kapsenberg et al 1991;Romagnani 1994). Human Th1 cell lines are known to express higher levels of CD26 protein than Th2 cell lines (Willheim et al 1997). Thus far, it is unknown how CD26 protein expression and DPPIV activity are regulated after T-cell activation and whether both functions of the molecule contribute to differences in Th1 and Th2 cell function.…”

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confidence: 99%

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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

Boonacker

Wierenga

Smits

et al. 2002

J Histochem Cytochem.

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S U M M A R Y CD26/DPPIV is a cell surface glycoprotein that functions both in signal transduction and as a proteolytic enzyme, dipeptidyl peptidase IV (DPPIV). To investigate how two separate functions of one molecule are regulated, we analyzed CD26 protein expression and DPPIV enzyme activity on living human T-helper 1 (Th1) and Th2 cells that express different levels of CD26/DPPIV. DPPIV activity was specifically determined with the synthetic fluorogenic substrate ala-pro-cresyl violet and CD26 protein expression was demonstrated with an FITC-conjugated CD26-specific antibody. Fluorescence of liberated cresyl violet (red) and FITC (green) was detected simultaneously on living T-cells using flow cytometry and spectrofluorometry. Th1 cells expressed three-to sixfold more CD26 protein than Th2 cells. The signal transduction function of the CD26/DPPIV complex, tested by measuring its co-stimulatory potential for proliferation, was directly related to the amount of CD26 protein at the cell surface. However, DPPIV activity was similar in both cell populations at physiological substrate concentrations because of differences in K m and V max values of DPPIV on Th1 and Th2 cells. Western blotting and zymography of Th1 and Th2 wholecell lysates demonstrated similar patterns. This study shows that two functions of one molecule can be controlled differentially.

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Section: Discussionmentioning

confidence: 99%

Section: Polarization Studiesmentioning

confidence: 99%

mentioning

confidence: 99%

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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

Boonacker

Wierenga

Smits

et al. 2002

J Histochem Cytochem.

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“…Flow cytometric assessment of T cell cytokine production was performed essentially according to the technique described by Jung and others 15 and modified by Willheim and others. 16 The PBMCs were isolated from heparinized blood by ficoll-diatrizoate centrifugation. Cells were then cultured in Ultra Culture Medium (Bio Whittaker, Walkersville, MD) supplemented with L-glutamine (2 mM; Sigma, St. Louis, MO), gentamicin (170 mg/L; Sigma), and 2-mercaptoethanol (3.5 l/L; Merck, Darmstadt, Germany) and stimulated with phorbol 12-myristate 13-acetate (10 ng/ml; Sigma) and ionomycin (1.25 M; Sigma) in the presence of monensin (1 M; Sigma) for 4 hr at 37ЊC in 5% CO 2 .…”

Section: Patientsmentioning

confidence: 99%

Increased frequency of Th2-type cytokine-producing T cells in microfilaremic loiasis.

Winkler

Willheim²,

Baier³

et al. 1999

The American Journal of Tropical Medicine and Hygiene

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Abstract. The frequency of cytokine-producing peripheral blood mononuclear cells was assessed in 28 subjects with microfilaremic loiasis and in 14 amicrofilaremic individuals. In addition, a subgroup of seven microfilaremic individuals coinfected with Plasmodium malariae was evaluated. By using flow cytometry for the intracellular detection of cytokines, a more pronounced T helper (Th)2 cell-type response with the expansion of interleukin (IL)-4, IL-10, and IL-13 expressing CD4 ϩ cells in the microfilaremic compared with the amicrofilaremic group was noted. Expression of IL-5 was equivalent in both groups as was the frequency of Th2-type cytokines expressing CD8 ϩ cells and of Th1-type cytokines (interferon [IFN]-␥, IL-2, IFN-␥/IL-2) producing CD4 ϩ and CD8 ϩ cells. Th0-type cytokineexpressing cells, represented by IL-4/IFN-␥, IL-10/IFN-␥, and IL-13/IFN-␥, were equally distributed within groups. Coinfection of P. malariae did not significantly alter the cytokine expression compared with microfilaremic individuals without P. malariae infections. By identifying a large panel of cytokine-producing T cell subpopulations, a Th2-driven immune response in microfilaremic Loa loa patients was noted.Loiasis is a parasitic infection caused by the filarial nematode Loa loa, which is endemic in rain forest areas of Central and West Africa. Infective larvae are transmitted by diurnal bites of flies of the genus Chrysops and, over a period of several months, develop into mature, adult worms that may liberate microfilariae into the bloodstream. Among individuals infected with L. loa, clinically distinct subgroups can be identified with manifestations ranging from asymptomatic microfilaremia to a hyperresponsive state characterized by more frequent episodes of local angioedema (Calabar swellings) and pronounced eosinophilia in the absence of microfilariae. In endemic areas, only a minority of infected people have detectable microfilariae in blood. 1 However, the majority of infected subjects, including most visitors to endemic areas, remain amicrofilaremic and are more likely to have a hyper-responsive syndrome. 2 The apparent differences in clinical presentation are thought to reflect the diversity of the immune response of the host to filarial antigen, with diminished humoral and cellular reactivity in the presence of circulating microfilariae. Most previous results on L. loa-host relationship were derived from studying temporary residents of areas of endemicity. These amicrofilaremic patients had elevated serum parasite-specific immunoglobulin (IgE and IgG) levels, augmented filaria-specific lymphocyte proliferative responses, and an increase in the ratio of CD4 ϩ /CD8 ϩ T cells. 3,4 Immune mechanisms activated in individuals continuously exposed to infection have been studied far more extensively in other filarial species. In particular, the categorization of T helper (Th) cells into at least two functionally different subsets on the basis of their cytokine profiles has provided a useful framework for the understanding of im...

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“…In tumour stroma, CD26 was not expressed by blood vessels, but could be detected in CD45-positive cells, albeit at low frequency. The contrast between CD26 levels in wounded dermis and tumour stroma could potentially reflect a switch from a pro-inflammatory Th1 environment in wounds to an anti-inflammatory/pro-tumor Th2 cytokine profile in papillomas (Willheim et al, 1997). In contrast to the observed downregulation of CD26, FAP-1, a CD26 family member, is expressed exclusively in the tumour stroma (Kraman et al, 2010).…”

Section: Discussionmentioning

confidence: 97%

Upregulation of CD26 expression in epithelial cells and stromal cells during wound-induced skin tumour formation

et al. 2011

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We have previously described InvEE transgenic mice in which non-dividing, differentiating epidermal cells express oncogenically activated MAPK kinase 1 (MEK1). Skin wounding triggers tumour formation in InvEE mice via a mechanism that involves epidermal release of IL-1a and attraction of a pro-tumorigenic inflammatory infiltrate. To look for potential effects on the underlying connective tissue, we screened InvEE and wild-type epidermis for differential expression of cytokines and immune modulators. We identified a single protein, CD26 (dipeptidyl peptidase-4). CD26 serum levels were not increased in InvEE mice. In contrast, CD26 was upregulated in keratinocytes expressing mutant MEK1 and in the epithelial compartment of InvEE tumours, where it accumulated at cell-cell borders. CD26 expression was increased in dermal fibroblasts following skin wounding but was downregulated in tumour stroma. CD26 activity was stimulated by calcium-induced intercellular adhesion in keratinocytes, suggesting that the upregulation of CD26 in InvEE epidermis is due to expansion of the differentiated cell layers. IL-1a treatment of dermal fibroblasts stimulated CD26 activity, and therefore epidermal IL-1a release may contribute to the upregulation of CD26 expression in wounded dermis. Pharmacological blockade of CD26, via Sitagliptin, reduced growth of InvEE tumours, while combined inhibition of IL-1a and CD26 delayed tumour onset and reduced tumour incidence. Our results demonstrate that inappropriate activation of MEK1 in the epidermis leads to changes in dermal fibroblasts that, like the skin inflammatory infiltrate, contribute to tumour formation.

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Cell surface characterization of T lymphocytes and allergen-specific T cell clones: Correlation of CD26 expression with T H1 subsets

Cited by 116 publications

References 36 publications

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

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

Increased frequency of Th2-type cytokine-producing T cells in microfilaremic loiasis.

Upregulation of CD26 expression in epithelial cells and stromal cells during wound-induced skin tumour formation

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