FOXP3+ CD4 T-cell maturity and responses to microbial stimulation alter with age and associate with early-life gut colonization Sophia Björkander, Maria.

Slides:

Advertisements

Similar presentations

Monica G. Lawrence, MD, Jennifer W. Leiding, MD, Jonathan J

Advertisements

Impaired TH17 responses in patients with chronic mucocutaneous candidiasis with and without autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy

Vitamin D3 treatment of vitamin D–insufficient asthmatic patients does not alter immune cell function Brandy Reid, MS, Pierre-Olivier Girodet, MD, PhD,

Topical application of a vitamin D3 analogue and corticosteroid to psoriasis plaques decreases skin infiltration of TH17 cells and their ex vivo expansion

Human group 2 innate lymphoid cells do not express the IL-5 receptor

Flow cytometry imaging identifies rare TH2 cells expressing thymic stromal lymphopoietin receptor in a “proallergic” milieu Amanda J. Reefer, MS, Kathryn.

Regulatory T cells as a biomarker for response to adalimumab in rheumatoid arthritis Dao X. Nguyen, BSc, Alice Cotton, RN, BSc, Laura Attipoe, MBBS, Coziana.

Correlation of allergen-specific T follicular helper cell counts with specific IgE levels and efficacy of allergen immunotherapy Yin Yao, MD, Cai-Ling.

Induction of anergic allergen-specific suppressor T cells using tolerogenic dendritic cells derived from children with allergies to house dust mites

Reduced TH1/TH17 CD4 T-cell numbers are associated with impaired purified protein derivative–specific cytokine responses in patients with HIV-1 infection

Cell-to-cell contact between activated CD4+ T lymphocytes and unprimed monocytes interferes with a TH1 response Miriam Wittmann, MD, Mareike Alter, Tanja.

Impaired TH17 responses in patients with chronic mucocutaneous candidiasis with and without autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy

Sytze de Roock, PhD, Arie J

Reduced IFN-γ receptor expression and attenuated IFN-γ response by dendritic cells in patients with atopic dermatitis Eva Gros, MSc, Susanne Petzold,

Predominance of type 2 cytokine–producing CD4+ and CD8+ cells in patients with atopic dermatitis Masatoshi Nakazawa, DVMa, Nakako Sugi, MDb, Hiroshi.

Human B cells promote T-cell plasticity to optimize antibody response by inducing coexpression of TH1/TFH signatures Jelle de Wit, PhD, Tineke Jorritsma,

Immunologic defects in 22q11.2 deletion syndrome

Toll-like receptor 7–induced naive human B-cell differentiation and immunoglobulin production Mark C. Glaum, MD, PhD, Shilpi Narula, MD, Decheng Song,

T-cell regulation during viral and nonviral asthma exacerbations

Penicillium marneffei infection and impaired IFN-γ immunity in humans with autosomal- dominant gain-of-phosphorylation STAT1 mutations Pamela P.W. Lee,

Topical application of a vitamin D3 analogue and corticosteroid to psoriasis plaques decreases skin infiltration of TH17 cells and their ex vivo expansion

Expansion of activated regulatory T cells inversely correlates with clinical severity in septic neonates Eleonora Timperi, PhD, Laura Folgori, MD, Donato.

Inhibition of differentiation, amplification, and function of human TH17 cells by intravenous immunoglobulin Mohan S. Maddur, DVM, Janakiraman Vani,

IL-2 consumption by highly activated CD8 T cells induces regulatory T-cell dysfunction in patients with hemophagocytic lymphohistiocytosis Stéphanie.

Jelle de Wit, PhD, Maarten E. Emmelot, BSc, Martien C. M

Differences in innate immune function between allergic and nonallergic children: New insights into immune ontogeny Meri K. Tulic, BSc, PhD, Megan Hodder,

Toll-like receptor 4 ligation enforces tolerogenic properties of oral mucosal Langerhans cells Jean-Pierre Allam, MD, Wen-Ming Peng, MSc, Torsten Appel,

Triggering of specific Toll-like receptors and proinflammatory cytokines breaks allergen- specific T-cell tolerance in human tonsils and peripheral blood

Flow cytometric measurement of STAT1 and STAT3 phosphorylation in CD4+ and CD8+ T cells—clinical applications in primary immunodeficiency diagnostics

Dawn C. Newcomb, PhD, Madison G

Cysteinyl leukotriene E4 activates human group 2 innate lymphoid cells and enhances the effect of prostaglandin D2 and epithelial cytokines Maryam Salimi,

Susan L. Prescott, PhD, MD, Paul Noakes, BSc (Hons), PhD, Bonita W. Y

Human IL-31 is induced by IL-4 and promotes TH2-driven inflammation

Clara cell 16-kd protein downregulates TH2 differentiation of human naive neonatal T cells Sofi Johansson, MSc, Göran Wennergren, MD, PhD, Nils Åberg,

Forkhead box protein 3 demethylation is associated with tolerance induction in peanut- induced intestinal allergy Meiqin Wang, MD, PhD, Ivana V. Yang,

Vitamin D3 treatment of vitamin D–insufficient asthmatic patients does not alter immune cell function Brandy Reid, MS, Pierre-Olivier Girodet, MD, PhD,

Decreased T-cell receptor signaling through CARD11 differentially compromises forkhead box protein 3–positive regulatory versus TH2 effector cells to.

Jovana Maric, MSc, Avinash Ravindran, MSc, Luca Mazzurana, MSc, Åsa K

Kathleen R. Bartemes, BA, Gail M. Kephart, BS, Stephanie J

Differential expression of functional chemokine receptors on human blood and lung group 2 innate lymphoid cells Cathryn A. Weston, PhD, Batika M.J. Rana,

Steroid resistance of airway type 2 innate lymphoid cells from patients with severe asthma: The role of thymic stromal lymphopoietin Sucai Liu, PhD,

Katherine G. MacDonald, BSc, Nicholas A. J

Neutrophils in antiretroviral therapy–controlled HIV demonstrate hyperactivation associated with a specific IL-17/IL-22 environment Laure Campillo-Gimenez,

Targeting Fel d 1 to FcγRI induces a novel variation of the TH2 response in subjects with cat allergy Kathryn E. Hulse, BS, Amanda J. Reefer, MS, Victor.

T-box 21 transcription factor is responsible for distorted TH2 differentiation in human peripheral CD4+ T cells Osamu Kaminuma, DVM, PhD, Fujiko Kitamura,

Inhibition of human B-cell development into plasmablasts by histone deacetylase inhibitor valproic acid Anne-Kathrin Kienzler, MSc, Marta Rizzi, MD,

Sandra Hellberg, MSc, Ratnesh B

Targeting allergen to FcγRI reveals a novel TH2 regulatory pathway linked to thymic stromal lymphopoietin receptor Kathryn E. Hulse, PhD, Amanda J. Reefer,

Patients with atopic dermatitis and history of eczema herpeticum elicit herpes simplex virus–specific type 2 immune responses Stephan Traidl, Petra Kienlin,

A thymic stromal lymphopoietin–responsive dendritic cell subset mediates allergic responses in the upper airway mucosa Guro R. Melum, MD, Lorant Farkas,

Benjamin T. Prince, MD, Msci, Ashley L. Devonshire, MD, MPH, Kristin A

Chronic cat allergen exposure induces a TH2 cell–dependent IgG4 response related to low sensitization Amedee Renand, PhD, Luis D. Archila, MSc, John.

Bet v 1–specific T-cell receptor/forkhead box protein 3 transgenic T cells suppress Bet v 1–specific T-cell effector function in an activation-dependent.

Peanut-specific type 1 regulatory T cells induced in vitro from allergic subjects are functionally impaired Laurence Pellerin, PhD, Jennifer Anne Jenks,

T-bet inhibits innate lymphoid cell–mediated eosinophilic airway inflammation by suppressing IL-9 production Ayako Matsuki, MD, Hiroaki Takatori, MD,

The relative contribution of IL-4 and IL-13 to human IgE synthesis induced by activated CD4+ or CD8+ T cells Juha Punnonen, MD, PhD, Hans Yssel, PhD,

T-bet inhibits innate lymphoid cell–mediated eosinophilic airway inflammation by suppressing IL-9 production Ayako Matsuki, MD, Hiroaki Takatori, MD,

The mannose receptor negatively modulates the Toll-like receptor 4–aryl hydrocarbon receptor–indoleamine 2,3-dioxygenase axis in dendritic cells affecting.

Staphylococcal exotoxins are strong inducers of IL-22: A potential role in atopic dermatitis Margarete Niebuhr, MD, Helena Scharonow, MS, Merle Gathmann,

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

In vivo maturation of TH cells in relation to atopy

Monica G. Lawrence, MD, Jennifer W. Leiding, MD, Jonathan J

Sara Paveglio, PhD, MS, Erin Bennett, MS, Kelly L. Hawley, PhD, Adam P

Foxp3+ Regulatory T Cells of Psoriasis Patients Easily Differentiate into IL-17A- Producing Cells and Are Found in Lesional Skin H. Jorn Bovenschen, Peter.

Human γ/δ T-cell proliferation and IFN-γ production induced by hexamethylene diisocyanate Adam V Wisnewski, PhD, Christina A Herrick, MD, PhD, Qing Liu,

Bone marrow transplantation for MHC class I deficiency corrects T-cell immunity but dissociates natural killer cell repertoire formation from function

Inhibition of human allergic T-cell responses by IL-10–treated dendritic cells: Differences from hydrocortisone-treated dendritic cells Iris Bellinghausen,

The mannose receptor negatively modulates the Toll-like receptor 4–aryl hydrocarbon receptor–indoleamine 2,3-dioxygenase axis in dendritic cells affecting.

Toll-like receptor heterodimer variants protect from childhood asthma

Invariant natural killer T cells from children with versus without food allergy exhibit differential responsiveness to milk-derived sphingomyelin Soma.

Presentation transcript:

FOXP3+ CD4 T-cell maturity and responses to microbial stimulation alter with age and associate with early-life gut colonization Sophia Björkander, Maria A. Johansson, PhD, Lena Hell, MSc, Gintare Lasaviciute, MSc, Caroline Nilsson, MD, PhD, Ulrika Holmlund, PhD, Eva Sverremark-Ekström, PhD Journal of Allergy and Clinical Immunology Volume 138, Issue 3, Pages 905-908.e4 (September 2016) DOI: 10.1016/j.jaci.2016.04.027 Copyright © 2016 The Authors Terms and Conditions

Fig 1 The phenotype and functional responses of CD4+CD25+FOXP3+CD127low cells mature with age. PBMC were analyzed after 2-hour resting (A and D) or after 24-hour stimulation with S aureus-CFS (B and E). Naive CD4+ T cells were cultured with autologous monocytes and analyzed after 48-hour stimulation with S aureus-CFS (C). Fig 1, A, Left: the percentage of CD25+FOXP3+CD127low (FOXP3+) cells among the CD4+ T-cell population. Middle and right: the percentages of CD45RA+ cells (middle) and HELIOS+ cells (right) among the FOXP3+ population. Fig 1, B, Upper left: the percentage of FOXP3+ cells among the CD4+ T-cell population; upper right and lower panels: the percentages of IL-10+, IFN-γ+, and IL-17A+ cells among the FOXP3+ population. Fig 1, C, Representative intracellular stainings of FOXP3 and T-bet expression in isolated naive CD4+ T cells or in CD4+ T cells in whole PBMCs. Fig 1, D, The percentage of CD161+ cells among the FOXP3+ population. Fig 1, E, The percentage of CD161+ cells and CD161 MFI values among the FOXP3+ population. CB, Cord blood; MFI, mean fluorescence intensity; T-bet, T-box transcription factor. ∗P < .05, ∗∗P ≤ .01, ∗∗∗P ≤ .001, and ∗∗∗∗P ≤ .0001. Journal of Allergy and Clinical Immunology 2016 138, 905-908.e4DOI: (10.1016/j.jaci.2016.04.027) Copyright © 2016 The Authors Terms and Conditions

Fig 2 Infant colonization with S aureus and lactobacilli associates with CD161 expression and cytokine production by FOXP3+ cells at 2 years of age. PBMC were analyzed after 2-hour resting (A and B) or after 24-hour stimulation with S aureus-CFS ± L reuteri-CFS (C-E). Immunological data at 2 years of age were correlated with the presence/absence of gut bacteria early in life (age 1 week, 2 weeks, 2 months). Fig 2, A and B, The percentage of CD161+ cells among the FOXP3+ population in 2-year-old children colonized (+) or not colonized (−) by S aureus or in correlation with the relative amounts of S aureus in stool expressed as percent bacterial DNA of total nucleic acids. Fig 2, C, The percentage of IL-10+ cells among the FOXP3+ population in correlation with the relative amounts of S aureus in stool. Fig 2, D, The percentage of FOXP3+ cells expressing IL-10, IFN-γ, and IL-17A. Fig 2, E, The percentage of IL-10+ cells among the FOXP3+ population in 2-year-old children in relation to lactobacilli colonization. ∗P < .05, ∗∗P ≤ .01, ∗∗∗P ≤ .001, and ∗∗∗∗P ≤ .0001. Journal of Allergy and Clinical Immunology 2016 138, 905-908.e4DOI: (10.1016/j.jaci.2016.04.027) Copyright © 2016 The Authors Terms and Conditions

Fig E1 Representative dot plots of flow cytometry data. A, PBMCs were rested for 2 hours before being stained and analyzed by flow cytometry. Left: staining of FOXP3 and CD25 gated from live CD4+ T cells; middle and right: staining of HELIOS (middle) and CD45RA (right) gated on CD4+CD25+FOXP3+CD127low cells. B, PBMCs were left unstimulated or cultured in the presence of S aureus 161:2-CFS. Representative staining of FOXP3 and CD25 exemplified by PBMCs from one 7-year-old donor. C, PBMCs were left unstimulated or cultured in the presence of S aureus-CFS. Representative intracellular staining of IL-10 expression in FOXP3+ cells. D, Representative intracellular stainings of ROR-γt and GATA-3 expression in isolated naive CD4 T cells cultured with autologous monocytes or in CD4 T cells in whole PBMCs after stimulation with S aureus 161:2-CFS. CB, Cord blood; FSC, forward scatter; GATA, trans-acting T-cell-specific transcription factor GATA-3; ROR, RAR-related orphan receptor. Journal of Allergy and Clinical Immunology 2016 138, 905-908.e4DOI: (10.1016/j.jaci.2016.04.027) Copyright © 2016 The Authors Terms and Conditions

Fig E2 The percentage of CD4+ and CD4+FOXP3− T-cells that express CD45RA, HELIOS, and CD161 alter with age. PBMC were rested for 2 hours before being stained and analyzed by flow cytometry. A-C, The percentage of CD45RA+ cells (Fig E2, A), HELIOS+ cells (Fig E2, B), and CD161+ cells (Fig E2, C) among the total CD4+ (left column) or the CD4+FOXP3− (right column) T-cell populations. CB, Cord blood. ∗P < .05, ∗∗P ≤ .01, ∗∗∗P ≤ .001, and ∗∗∗∗P ≤ .0001. Journal of Allergy and Clinical Immunology 2016 138, 905-908.e4DOI: (10.1016/j.jaci.2016.04.027) Copyright © 2016 The Authors Terms and Conditions

Fig E3 L reuteri-CFS dampen S aureus-CFS–induced cytokine production. PBMCs were left unstimulated or cultured in the presence of S aureus-CFS ± L reuteri-CFS. A, The percentage of CD161+ cells among the FOXP3+ population. B, Representative intracellular staining of IL-10 expression in FOXP3+ cells. C, Secreted levels of IL-10, IFN-γ, and IL-17A in PBMC cultures measured with ELISA. Secreted levels of all cytokines at unstimulated conditions were with no exceptions below the detection limits (not shown). FSC, Forward scatter. ∗P < .05, ∗∗P ≤ .01, ∗∗∗P ≤ .001, and ∗∗∗∗P ≤ .0001. Journal of Allergy and Clinical Immunology 2016 138, 905-908.e4DOI: (10.1016/j.jaci.2016.04.027) Copyright © 2016 The Authors Terms and Conditions