P026. Characterisation of mucosal CD4+ T-cells in peripheral blood of healthy controls and paediatric inflammatory bowel disease patients

Treg modulation has been hypothesized as one of the mechanisms by which antitumor necrosis factorα(TNFα) agents exert their action in rheumatoid arthritis (RA) and inflammatory bowel disease (IBD). However, data in IBD are still conflicting. We evaluated CD4+CD25+FOXP3+(Tregs) by flow cytometry in peripheral blood from 32 adult IBD patient before (T0) and after the induction of anti-TNFαtherapy (T1). Eight healthy controls (HCs) were included. We also evaluated the number of FOXP3+cells in the lamina propria (LP) in biopsies taken in a subset of patients and controls. Treg frequencies were significantly increased in peripheral blood from our patients after anti-TNFαtherapy compared to T0. T1 but not T0 levels were higher than HC. The increase was detectable only in clinical responders to the treatment. A negative correlation was found among delta Treg levels and the age of patients or disease duration and with the activity score of Crohn’s disease (CD). No significant differences were found in LP FOXP3+cells. Our data suggest the possibility that in IBD patients the treatment with anti-TNFαmay affect Treg percentages and that Treg modifications may correlate with clinical response, but differently in early versus late disease.

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Exclusive increase of CX3CR1+CD28−CD4+ T cells in inflammatory bowel disease and their recruitment as intraepithelial lymphocytes

Inflammatory Bowel Diseases ◽

10.1002/ibd.20113 ◽

2007 ◽

Vol 13 (7) ◽

pp. 837-846 ◽

Cited By ~ 54

Author(s):

Taku Kobayashi ◽

Susumu Okamoto ◽

Yuko Iwakami ◽

Atsushi Nakazawa ◽

Tadakazu Hisamatsu ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

T Cells ◽

Bowel Disease ◽

Cd4 T Cells ◽

Intraepithelial Lymphocytes ◽

Inflammatory Bowel

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IL-10 signaling in dendritic cells controls IL-1β-mediated IFNγ secretion by human CD4+ T cells: relevance to inflammatory bowel disease

Mucosal Immunology ◽

10.1038/s41385-019-0194-9 ◽

2019 ◽

Vol 12 (5) ◽

pp. 1201-1211 ◽

Cited By ~ 10

Author(s):

S. Veenbergen ◽

P. Li ◽

H. C. Raatgeep ◽

D. J. Lindenbergh-Kortleve ◽

Y. Simons-Oosterhuis ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

T Cells ◽

Dendritic Cells ◽

Bowel Disease ◽

Cd4 T Cells ◽

Inflammatory Bowel

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Peripheral and Intestinal CD4+ T Cells With a Regulatory Phenotype in Pediatric Patients With Inflammatory Bowel Disease

Journal of Pediatric Gastroenterology and Nutrition ◽

10.1097/mpg.0b013e3181e4d323 ◽

2010 ◽

Vol 51 (5) ◽

pp. 563-572 ◽

Cited By ~ 11

Author(s):

Raffaella La Scaleia ◽

Stefania Morrone ◽

Antonella Stoppacciaro ◽

Stefania Scarpino ◽

Manila Antonelli ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

T Cells ◽

Bowel Disease ◽

Cd4 T Cells ◽

Pediatric Patients ◽

Inflammatory Bowel ◽

Regulatory Phenotype

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The Mechanisms of Up-Regulation of K+ Channels in CD4+ T Cells of Inflammatory Bowel Disease

Biophysical Journal ◽

10.1016/j.bpj.2019.11.2369 ◽

2020 ◽

Vol 118 (3) ◽

pp. 420a

Author(s):

Susumu Ohya ◽

Kyoko Endo ◽

Hiroaki Kito ◽

Junko Kajikuri ◽

Takayoshi Suzuki

Keyword(s):

Inflammatory Bowel Disease ◽

T Cells ◽

Bowel Disease ◽

Cd4 T Cells ◽

K Channels ◽

Inflammatory Bowel

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Ontogeny, function, and peripheral homeostasis of regulatory T cells in the absence of interleukin-7

Blood ◽

10.1182/blood-2006-04-017947 ◽

2006 ◽

Vol 108 (7) ◽

pp. 2300-2306 ◽

Cited By ~ 33

Author(s):

Régis Peffault de Latour ◽

Hélène C. Dujardin ◽

Florence Mishellany ◽

Odile Burlen-Defranoux ◽

Julien Zuber ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

T Cells ◽

T Cell ◽

Bowel Disease ◽

Cd4 T Cells ◽

Cell Subset ◽

Thymic Involution ◽

Cell Compartment ◽

Interleukin 7 ◽

Inflammatory Bowel

Abstract Mice lacking interleukin-7 (IL-7–/– mice) have no signs of autoimmune disease, contrary to other models of lymphopenia. We investigated whether the absence of disease was due to the fact that IL-7 is dispensable for the ontogeny, function, and homeostasis of regulatory CD4+ T cells. We show here that the establishment of the peripheral pool of Foxp3-expressing regulatory cells is IL-7 independent, and the premature involution of the thymus in IL-7–/– mice does not change the representation of the CD4+CD25+ T-cell compartment. In addition, CD4+CD25+ T cells expand in the absence of IL-7, without losing Foxp3 expression. The frequency of activated peripheral CD4+ T cells increases with age in both the CD25– and CD25+ compartments, with the CD4+CD25+ T cells displaying signs of constant activation. IL-7–/– CD4+CD25+ T cells control inflammatory bowel disease induced by IL-7–/– T cells even in hosts lacking IL-7. Depletion of the CD25+ T-cell subset after thymic involution results in a mild form of inflammatory bowel disease (IBD), which resolves concomitantly with the regeneration of this subset. This study shows for the first time that IL-7–/– mice have a robust regulatory Foxp3-expressing CD4+ T-cell compartment that controls T-cell–mediated disease. It also highlights the potential of the regulatory Foxp3-expressing CD4+CD25– T-cell population to restore a functional CD4+CD25+ T-cell compartment through an IL-7–independent pathway.

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Deficiency of the Intestinal Growth Factor, Glucagon-Like Peptide 2, in the Colon of SCID Mice with Inflammatory Bowel Disease Induced by Transplantation of CD4+ T Cells

Scandinavian Journal of Gastroenterology ◽

10.1080/003655200750023796 ◽

2000 ◽

Vol 35 (5) ◽

pp. 522-527 ◽

Cited By ~ 21

Author(s):

P. T. Schmidt, B. Hartmann, S. Breg

Keyword(s):

Inflammatory Bowel Disease ◽

T Cells ◽

Growth Factor ◽

Bowel Disease ◽

Cd4 T Cells ◽

Scid Mice ◽

Intestinal Growth ◽

Inflammatory Bowel ◽

Glucagon Like Peptide

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Intestinal CD103+CD4+ and CD103+CD8+ T-Cell Subsets in the Gut of Inflammatory Bowel Disease Patients at Diagnosis and During Follow-up

Inflammatory Bowel Diseases ◽

10.1093/ibd/izz049 ◽

2019 ◽

Vol 25 (9) ◽

pp. 1497-1509 ◽

Cited By ~ 8

Author(s):

Britt Roosenboom ◽

Peter J Wahab ◽

Carolijn Smids ◽

Marcel J M Groenen ◽

Elly van Koolwijk ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

T Cells ◽

T Cell ◽

Bowel Disease ◽

Cd8 T Cell ◽

T Cell Subsets ◽

Healthy Controls ◽

Inflammatory Bowel ◽

Active Inflammation

Abstract Background The integrin CD103 is proposed to be a potential therapeutical target in inflammatory bowel disease (IBD), as it can form a heterodimeric integrin with β7 (Etrolizumab, anti-β7 integrin) on epithelial T cells. Therefore, we aimed to study the frequencies of different intestinal CD103+T-cell subsets, both CD4+ and CD8+, in newly diagnosed, untreated IBD patients at baseline and during follow-up, compared with healthy controls. Methods Intestinal biopsies from inflamed segments during colonoscopy and peripheral blood samples were prospectively taken from IBD patients at diagnosis and during follow-up. Blood and single cell suspensions from biopsies were analyzed for CD103+ T-cell subpopulations by flow cytometry and expressed as median percentages of the total T-cell population. Results In total, 75 Crohn’s disease (CD) patients, 49 ulcerative colitis (UC) patients, and 16 healthy controls were included. At presentation, IBD patients displayed lower percentages of CD103+T-cell subsets in inflamed biopsies: 3% (1 to 5) CD103+CD4+ in IBD vs 5% (5 to 7) in healthy controls (P = 0.007) and 9% (4 to 15) CD103+CD8+ compared with 42% (23 to 57) in healthy controls (P = 0.001). The majority of intestinal T cells was composed of CD103-CD4+ T cells (65% [52 to 74]) in IBD compared with 30% (21 to 50) in healthy controls (P = 0.001). In patients with endoscopic remission during follow-up (n = 27), frequencies of CD103+ and CD103-T-cell subsets were comparable with healthy controls. Conclusion At diagnosis, active inflammation in IBD was associated with decreased percentages of both CD103+CD4+ and CD103+CD8+T-cell subsets in colon and ileum biopsies. In active disease during follow-up, these T-cell populations remained low but increased in remission to values comparable with healthy controls. A shift toward more CD103-T cells was observed during active inflammation.

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