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

Autor: Joosse ME; Laboratory of Pediatrics, division Gastroenterology and Nutrition, Erasmus University Medical Center-Sophia Children's Hospital, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands., Menckeberg CL; Laboratory of Pediatrics, division Gastroenterology and Nutrition, Erasmus University Medical Center-Sophia Children's Hospital, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands., de Ruiter LF; Laboratory of Pediatrics, division Gastroenterology and Nutrition, Erasmus University Medical Center-Sophia Children's Hospital, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands., Raatgeep HRC; Laboratory of Pediatrics, division Gastroenterology and Nutrition, Erasmus University Medical Center-Sophia Children's Hospital, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands., van Berkel LA; Laboratory of Pediatrics, division Gastroenterology and Nutrition, Erasmus University Medical Center-Sophia Children's Hospital, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands., Simons-Oosterhuis Y; Laboratory of Pediatrics, division Gastroenterology and Nutrition, Erasmus University Medical Center-Sophia Children's Hospital, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands., Tindemans I; Laboratory of Pediatrics, division Gastroenterology and Nutrition, Erasmus University Medical Center-Sophia Children's Hospital, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands., Muskens AFM; Department of Pulmonology, Erasmus University Medical Center, 3000 CA Rotterdam, The Netherlands., Hendriks RW; Department of Pulmonology, Erasmus University Medical Center, 3000 CA Rotterdam, The Netherlands., Hoogenboezem RM; Department of Hematology, Erasmus University Medical Center, 3000 CA Rotterdam, The Netherlands., Cupedo T; Department of Hematology, Erasmus University Medical Center, 3000 CA Rotterdam, The Netherlands., de Ridder L; Department of Pediatric Gastroenterology, Erasmus University Medical Center-Sophia Children's Hospital, 3000 CA Rotterdam, The Netherlands., Escher JC; Department of Pediatric Gastroenterology, Erasmus University Medical Center-Sophia Children's Hospital, 3000 CA Rotterdam, The Netherlands., Veenbergen S; Laboratory of Pediatrics, division Gastroenterology and Nutrition, Erasmus University Medical Center-Sophia Children's Hospital, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands., Samsom JN; Laboratory of Pediatrics, division Gastroenterology and Nutrition, Erasmus University Medical Center-Sophia Children's Hospital, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands. j.samsom@erasmusmc.nl.
Jazyk: angličtina
Zdroj: Mucosal immunology [Mucosal Immunol] 2019 Jan; Vol. 12 (1), pp. 154-163. Date of Electronic Publication: 2018 Aug 20.
DOI: 10.1038/s41385-018-0078-4
Abstrakt: 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 (CD62L neg CD4 + ) 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 CD38 neg 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 + CD45RA neg 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.
Databáze: MEDLINE
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