Induction of IL-10+CD4+CD25+ T cells by grass pollen immunotherapy

James N Francis; Stephen J Till; Stephen R Durham

doi:10.1067/mai.2003.1570

Induction of IL-10+CD4+CD25+ T cells by grass pollen immunotherapy

James N Francis, Stephen J Till, Stephen R Durham

Research output: Contribution to journal › Article › peer-review

486 Citations (Scopus)

Abstract

Background: Immunotherapy involves the modulation of allergen-specific T-cell responses, either TH2-to-TH1 immune deviation or, in bee venom-treated patients, induction of IL-10 production by CD4+CD25+ T cells. IL-10-producing CD4+CD25+ regulatory T cells have emerged as potential mediators of immune tolerance in numerous murine models of immunopathology. Objective: The aim of this study was to evaluate the role of IL-10 production and CD4+CD25+ T cells in the response to grass pollen immunotherapy. Methods: PBMCs were isolated from patients after 1 year of grass pollen immunotherapy and from matched untreated atopic and healthy control subjects. After 6 days of in vitro stimulation with Phleum pratense , production of IL-10, IL-5, IL-4, and IFN-γ and proliferation and numbers of CD4+CD25+ T cells were measured. T cells were then stimulated for a further 5 hours with phorbol 12-myristate 13-acetate and ionomycin and assessed for intracellular IL-10 by means of flow cytometry. Results: Patients undergoing immunotherapy produced significantly more IL-10 than atopic control subjects (patients undergoing immunotherapy, 116 ± 21 pg/mL [n = 11]; atopic patients, 30 ± 5 pg/mL [n = 11]; P < .001), and the number of CD4+CD25+ cells identified after allergen stimulation was also greater in the immunotherapy group. The numbers of CD4+CD25+ T cells correlated positively with activation as measured by proliferation in both of the control groups but not in the immunotherapy group. Moreover, only T cells from patients undergoing immunotherapy were positive for intracellular IL-10, and these were almost exclusively CD4+CD25+ cells. Conclusion: Grass pollen immunotherapy results in a population of circulating T cells that express the IL-10+CD4+CD25+ phenotype in response to allergen restimulation.

Original language	English
Pages (from-to)	1255-1261
Number of pages	7
Journal	Journal of Allergy and Clinical Immunology
Volume	111
Issue number	6
DOIs	https://doi.org/10.1067/mai.2003.1570
Publication status	Published - Jun 2003

Keywords

Interleukin-10
Humans
Desensitization, Immunologic
Receptors, Interleukin-2
Pollen
CD4-Positive T-Lymphocytes
Lymphocyte Activation
Cells, Cultured
Rhinitis, Allergic, Seasonal
Allergens
Poaceae
Adult
Cytokines
Immunophenotyping
Female
Male

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10.1067/mai.2003.1570

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@article{fecb0402c56d4ac5a918bf4de70106b4,

title = "Induction of IL-10+CD4+CD25+ T cells by grass pollen immunotherapy",

abstract = "Background: Immunotherapy involves the modulation of allergen-specific T-cell responses, either TH2-to-TH1 immune deviation or, in bee venom-treated patients, induction of IL-10 production by CD4+CD25+ T cells. IL-10-producing CD4+CD25+ regulatory T cells have emerged as potential mediators of immune tolerance in numerous murine models of immunopathology. Objective: The aim of this study was to evaluate the role of IL-10 production and CD4+CD25+ T cells in the response to grass pollen immunotherapy. Methods: PBMCs were isolated from patients after 1 year of grass pollen immunotherapy and from matched untreated atopic and healthy control subjects. After 6 days of in vitro stimulation with Phleum pratense , production of IL-10, IL-5, IL-4, and IFN-γ and proliferation and numbers of CD4+CD25+ T cells were measured. T cells were then stimulated for a further 5 hours with phorbol 12-myristate 13-acetate and ionomycin and assessed for intracellular IL-10 by means of flow cytometry. Results: Patients undergoing immunotherapy produced significantly more IL-10 than atopic control subjects (patients undergoing immunotherapy, 116 ± 21 pg/mL [n = 11]; atopic patients, 30 ± 5 pg/mL [n = 11]; P < .001), and the number of CD4+CD25+ cells identified after allergen stimulation was also greater in the immunotherapy group. The numbers of CD4+CD25+ T cells correlated positively with activation as measured by proliferation in both of the control groups but not in the immunotherapy group. Moreover, only T cells from patients undergoing immunotherapy were positive for intracellular IL-10, and these were almost exclusively CD4+CD25+ cells. Conclusion: Grass pollen immunotherapy results in a population of circulating T cells that express the IL-10+CD4+CD25+ phenotype in response to allergen restimulation.",

keywords = "Interleukin-10, Humans, Desensitization, Immunologic, Receptors, Interleukin-2, Pollen, CD4-Positive T-Lymphocytes, Lymphocyte Activation, Cells, Cultured, Rhinitis, Allergic, Seasonal, Allergens, Poaceae, Adult, Cytokines, Immunophenotyping, Female, Male",

author = "Francis, {James N} and Till, {Stephen J} and Durham, {Stephen R}",

year = "2003",

month = jun,

doi = "10.1067/mai.2003.1570",

language = "English",

volume = "111",

pages = "1255--1261",

journal = "Journal of Allergy and Clinical Immunology",

issn = "0091-6749",

publisher = "Elsevier",

number = "6",

}

TY - JOUR

T1 - Induction of IL-10+CD4+CD25+ T cells by grass pollen immunotherapy

AU - Francis, James N

AU - Till, Stephen J

AU - Durham, Stephen R

PY - 2003/6

Y1 - 2003/6

N2 - Background: Immunotherapy involves the modulation of allergen-specific T-cell responses, either TH2-to-TH1 immune deviation or, in bee venom-treated patients, induction of IL-10 production by CD4+CD25+ T cells. IL-10-producing CD4+CD25+ regulatory T cells have emerged as potential mediators of immune tolerance in numerous murine models of immunopathology. Objective: The aim of this study was to evaluate the role of IL-10 production and CD4+CD25+ T cells in the response to grass pollen immunotherapy. Methods: PBMCs were isolated from patients after 1 year of grass pollen immunotherapy and from matched untreated atopic and healthy control subjects. After 6 days of in vitro stimulation with Phleum pratense , production of IL-10, IL-5, IL-4, and IFN-γ and proliferation and numbers of CD4+CD25+ T cells were measured. T cells were then stimulated for a further 5 hours with phorbol 12-myristate 13-acetate and ionomycin and assessed for intracellular IL-10 by means of flow cytometry. Results: Patients undergoing immunotherapy produced significantly more IL-10 than atopic control subjects (patients undergoing immunotherapy, 116 ± 21 pg/mL [n = 11]; atopic patients, 30 ± 5 pg/mL [n = 11]; P < .001), and the number of CD4+CD25+ cells identified after allergen stimulation was also greater in the immunotherapy group. The numbers of CD4+CD25+ T cells correlated positively with activation as measured by proliferation in both of the control groups but not in the immunotherapy group. Moreover, only T cells from patients undergoing immunotherapy were positive for intracellular IL-10, and these were almost exclusively CD4+CD25+ cells. Conclusion: Grass pollen immunotherapy results in a population of circulating T cells that express the IL-10+CD4+CD25+ phenotype in response to allergen restimulation.

AB - Background: Immunotherapy involves the modulation of allergen-specific T-cell responses, either TH2-to-TH1 immune deviation or, in bee venom-treated patients, induction of IL-10 production by CD4+CD25+ T cells. IL-10-producing CD4+CD25+ regulatory T cells have emerged as potential mediators of immune tolerance in numerous murine models of immunopathology. Objective: The aim of this study was to evaluate the role of IL-10 production and CD4+CD25+ T cells in the response to grass pollen immunotherapy. Methods: PBMCs were isolated from patients after 1 year of grass pollen immunotherapy and from matched untreated atopic and healthy control subjects. After 6 days of in vitro stimulation with Phleum pratense , production of IL-10, IL-5, IL-4, and IFN-γ and proliferation and numbers of CD4+CD25+ T cells were measured. T cells were then stimulated for a further 5 hours with phorbol 12-myristate 13-acetate and ionomycin and assessed for intracellular IL-10 by means of flow cytometry. Results: Patients undergoing immunotherapy produced significantly more IL-10 than atopic control subjects (patients undergoing immunotherapy, 116 ± 21 pg/mL [n = 11]; atopic patients, 30 ± 5 pg/mL [n = 11]; P < .001), and the number of CD4+CD25+ cells identified after allergen stimulation was also greater in the immunotherapy group. The numbers of CD4+CD25+ T cells correlated positively with activation as measured by proliferation in both of the control groups but not in the immunotherapy group. Moreover, only T cells from patients undergoing immunotherapy were positive for intracellular IL-10, and these were almost exclusively CD4+CD25+ cells. Conclusion: Grass pollen immunotherapy results in a population of circulating T cells that express the IL-10+CD4+CD25+ phenotype in response to allergen restimulation.

KW - Interleukin-10

KW - Humans

KW - Desensitization, Immunologic

KW - Receptors, Interleukin-2

KW - Pollen

KW - CD4-Positive T-Lymphocytes

KW - Lymphocyte Activation

KW - Cells, Cultured

KW - Rhinitis, Allergic, Seasonal

KW - Allergens

KW - Poaceae

KW - Adult

KW - Cytokines

KW - Immunophenotyping

KW - Female

KW - Male

U2 - 10.1067/mai.2003.1570

DO - 10.1067/mai.2003.1570

M3 - Article

C2 - 12789226

SN - 0091-6749

VL - 111

SP - 1255

EP - 1261

JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

IS - 6

ER -

Induction of IL-10+CD4+CD25+ T cells by grass pollen immunotherapy

Abstract

Keywords

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