학술논문
Distinct CRTH2+CD161+ (peTh2) memory CD4+ T-cell cytokine profiles in food allergy and eosinophilic gastrointestinal disorders.
Document Type
Academic Journal
Author
Makiya MA; Human Eosinophil Section, LPD, NIAID, NIH, Bethesda, Maryland, USA.; Brown T; Clinical Parasitology Section, LPD, NIAID, NIH, Bethesda, Maryland, USA.; Holland N; Clinical Parasitology Section, LPD, NIAID, NIH, Bethesda, Maryland, USA.; Wetzler L; Clinical Parasitology Section, LPD, NIAID, NIH, Bethesda, Maryland, USA.; Ware JM; Clinical Parasitology Section, LPD, NIAID, NIH, Bethesda, Maryland, USA.; Khoury P; Human Eosinophil Section, LPD, NIAID, NIH, Bethesda, Maryland, USA.; Frischmeyer-Guerrerio PA; Food Allergy Research Section, LAD, NAID, NIH, Bethesda, Maryland, USA.; Klion AD; Human Eosinophil Section, LPD, NIAID, NIH, Bethesda, Maryland, USA.; Kuang FL; Human Eosinophil Section, LPD, NIAID, NIH, Bethesda, Maryland, USA.; Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Source
Publisher: Blackwell Scientific Publications Country of Publication: England NLM ID: 8906443 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1365-2222 (Electronic) Linking ISSN: 09547894 NLM ISO Abbreviation: Clin Exp Allergy Subsets: MEDLINE
Subject
Language
English
Abstract
Introduction: Although IgE-mediated food allergy (FA) and eosinophilic gastrointestinal disorders (EGID) are clinically distinct and treated differently, pathogenic effector Th2 (peTh2) cells are implicated in the pathogenesis of both FA and EGID. The aim of this study was to better characterize peTh2 cells in the context of FA and EGID and the overlap between these two conditions.
Methods: Peripheral blood peTh2 cells (CD3+CD4+CD27-CD49d+CRTH2+CD161+) were profiled by intracellular cytokine flow cytometry in the following patient cohorts: patients with FA alone (n = 8), FA and food-triggered EGID (EGID+FA+FT, n = 7), food-triggered EGID alone (EGID+FT, n = 7), EGID without FA or specific food triggers (ONLY_EGID, n = 9), and healthy volunteers (HV, n = 7). Overnight peripheral blood mononuclear cell (PBMC) culture supernatants were assessed for cytokine production by multiplex analysis.
Results: CRTH2+CD161+ (peTh2) memory CD4+ T cells were significantly increased in both patients with FA and those with ALL_EGID (inclusive of EGID+FA+FT, EGID+FT and ONLY_EGID) when compared to HV. However, ALL_EGID patients, particularly those with EGID+FA+FT, had significantly elevated IL-5+IL-13+ peTh2 cells, whereas FA patients had significantly elevated IFN-γ or IL-17A-expressing peTh2 cells. This finding was supported by increased spontaneous IL-5 and IL-13 production in overnight cultures of PBMC from EGID+FA+FT patients compared to spontaneous IL-10 and IFN-γ production by PBMC from FA patients. FA patients had increased IL-9, IL-10, IL-17A, and IFN-γ production in overnight cultures of stimulated PBMC.
Conclusions: EGID and IgE-mediated FA share a common cell subtype defined by specific surface markers and termed CRTH2+CD161+ (peTh2) memory CD4+ T cells. However, the cytokine profiles of these CRTH2+CD161+ (peTh2) memory CD4+ T cells are markedly different between the two disorders.
(Published 2023. This article is a U.S. Government work and is in the public domain in the USA.)
Methods: Peripheral blood peTh2 cells (CD3+CD4+CD27-CD49d+CRTH2+CD161+) were profiled by intracellular cytokine flow cytometry in the following patient cohorts: patients with FA alone (n = 8), FA and food-triggered EGID (EGID+FA+FT, n = 7), food-triggered EGID alone (EGID+FT, n = 7), EGID without FA or specific food triggers (ONLY_EGID, n = 9), and healthy volunteers (HV, n = 7). Overnight peripheral blood mononuclear cell (PBMC) culture supernatants were assessed for cytokine production by multiplex analysis.
Results: CRTH2+CD161+ (peTh2) memory CD4+ T cells were significantly increased in both patients with FA and those with ALL_EGID (inclusive of EGID+FA+FT, EGID+FT and ONLY_EGID) when compared to HV. However, ALL_EGID patients, particularly those with EGID+FA+FT, had significantly elevated IL-5+IL-13+ peTh2 cells, whereas FA patients had significantly elevated IFN-γ or IL-17A-expressing peTh2 cells. This finding was supported by increased spontaneous IL-5 and IL-13 production in overnight cultures of PBMC from EGID+FA+FT patients compared to spontaneous IL-10 and IFN-γ production by PBMC from FA patients. FA patients had increased IL-9, IL-10, IL-17A, and IFN-γ production in overnight cultures of stimulated PBMC.
Conclusions: EGID and IgE-mediated FA share a common cell subtype defined by specific surface markers and termed CRTH2+CD161+ (peTh2) memory CD4+ T cells. However, the cytokine profiles of these CRTH2+CD161+ (peTh2) memory CD4+ T cells are markedly different between the two disorders.
(Published 2023. This article is a U.S. Government work and is in the public domain in the USA.)