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Frequencies of circulating regulatory TIGIT+CD38+ effector T cells correlate with the course of inflammatory bowel disease

Mucosal Immunologyvolume 12pages154163 (2019) | Download Citation



Disease heterogeneity hampers achieving long-term disease remission in inflammatory bowel disease (IBD). Monitoring ongoing tissue-localized regulatory and inflammatory T-cell responses in peripheral blood would empower disease classification. We determined whether regulatory and inflammatory phenotypes of circulating CD38+ effector (CD62LnegCD4+) T cells, a population enriched for cells with mucosal antigen specificity, classify disease course in pediatric IBD patients. In healthy individuals, circulating CD38+ effector T cells had a predominant regulatory component with lower frequencies of IFNγ-secreting T cells, higher frequencies of IL-10-secreting T cells and higher frequencies of inhibitory molecule T-cell immunoglobulin and ITIM domain+ (TIGIT) cells than CD38neg effector T cells. TIGIT expression was stable upon stimulation and marked CD38+ T cells with inhibitory properties. In IBD patients with active intestinal inflammation this predominant regulatory component was lost: circulating CD38+ effector T cells had increased activated CD25+CD45RAneg and decreased TIGIT+ cell frequencies. TIGIT percentages below 25% before treatment associated with shorter duration of clinical remission. In conclusion, phenotypic changes in circulating CD38+ effector T cells, in particular the frequency of TIGIT+ cells, classify pediatric IBD patients and predict severity of disease course. These findings have relevance for IBD and can be exploited in graft-versus-host-disease and checkpoint inhibitor-induced inflammation in cancer.

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M.J. was supported by the Netherlands Organisation for Scientific Research grant 2013/09420/BOO; C.M., L.F.dR., and S.V. were funded by Dutch Sophia Research Foundation research grants S13-19, 671 and S14-17 respectively. Crocokids and the European Crohn’s and Colitis Organisation financially supported experimental costs. We thank Jessie M. Hulst and Barbara A.E. de Koning for contributing patient samples and Merel A. van Pieterson and Martha A. van Gaalen for study coordination. We thank the IBD patients and their families for participating and supporting our research.

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  1. Laboratory of Pediatrics, division Gastroenterology and Nutrition, Erasmus University Medical Center-Sophia Children’s Hospital, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands

    • Maria E. Joosse
    • , Celia L. Menckeberg
    • , Lilian F. de Ruiter
    • , H. (Rolien) C. Raatgeep
    • , Lisette A. van Berkel
    • , Ytje Simons-Oosterhuis
    • , Irma Tindemans
    • , Sharon Veenbergen
    •  & Janneke N. Samsom
  2. Department of Pulmonology, Erasmus University Medical Center, 3000 CA Rotterdam, The Netherlands

    • A. (Femke) M. Muskens
    •  & Rudi W. Hendriks
  3. Department of Hematology, Erasmus University Medical Center, 3000 CA Rotterdam, The Netherlands

    • Remco M. Hoogenboezem
    •  & Tom Cupedo
  4. Department of Pediatric Gastroenterology, Erasmus University Medical Center-Sophia Children’s Hospital, 3000 CA Rotterdam, The Netherlands

    • Lissy de Ridder
    •  & Johanna C. Escher


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M.J. and J.S. contributed to study concept and design, interpretation of data, and drafting of the manuscript. M.J. designed, conducted, and analyzed experiments. R.H., T.C., and S.V. contributed to sequencing data analysis and interpretation. C.M., L.F.dR., H.R., L.vB., Y.S., and F.M. performed experiments and data analysis. R.H., T.C., and S.V. provided important intellectual content. L.dR. and J.C.E. contributed important intellectual content and contributed the patient-sample collection. J.S. conceived the project, obtained funding and had full responsibility for the study.

Competing interests

The authors declare no competing interests.

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Correspondence to Janneke N. Samsom.

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