Costimulation through CD86 is involved in airway antigen-presenting cell and T cell responses to allergen in atopic asthmatics

M Larché; S J Till; B M Haselden; J North; J Barkans; C J Corrigan; A B Kay; D S Robinson

Costimulation through CD86 is involved in airway antigen-presenting cell and T cell responses to allergen in atopic asthmatics

M Larché, S J Till, B M Haselden, J North, J Barkans, C J Corrigan, A B Kay, D S Robinson

King's College London

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108 Citations (Scopus)

Abstract

Atopic allergic asthma is characterized by activation of Th2-type T cells in the bronchial mucosa. Previous reports have suggested an important role for costimulation through the CD28/CTLA4-CD80/CD86 pathway in allergen activation of T cells in animal models of inhaled allergen challenge. However, human allergen-specific lines and clones were reported to be costimulation independent. We therefore examined CD80 and CD86 dependence of allergen-induced T cell proliferation and cytokine production in peripheral blood and bronchoalveolar lavage from atopic asthmatic subjects and controls. Both allergen-induced proliferation and IL-5 production from PBMC were inhibited by CTLA4-Ig fusion protein and anti-CD86, but not anti-CD80 mAbs. When allergen-specific CD4+ T cell lines from peripheral blood were examined, proliferation and cytokine production were found to be independent of CD80 or CD86 costimulation. However, when cells obtained directly from the airways were examined, allergen-induced proliferation of bronchoalveolar lavage T cells from atopic asthmatic subjects was inhibited by anti-CD86 but not anti-CD80. In addition, bronchoalveolar lavage-adherent cells from asthmatic, but not control subjects showed APC activity to autologous T cells. This was also inhibited by anti-CD86 but not anti-CD80. Thus allergen-induced T cell activation and IL-5 production in the airway in asthmatic subjects is susceptible to blockade by agents interfering with costimulation via CD86, and this may hold therapeutic potential in asthma.

Original language	English
Pages (from-to)	6375-82
Number of pages	8
Journal	Journal of Immunology
Volume	161
Issue number	11
Publication status	Published - 1 Dec 1998

Keywords

Antigens, Differentiation
Membrane Glycoproteins
Humans
Antigens, CD45
Lymphocyte Activation
Antibodies, Monoclonal
Antigens, CD
Allergens
Bronchoalveolar Lavage Fluid
Adult
Cytokines
Male
Immunoconjugates
Antigen Presentation
Leukocytes, Mononuclear
Asthma
Antigens, CD86
Immunosuppressive Agents
CD4-Positive T-Lymphocytes
CTLA-4 Antigen
Bronchi
Interleukin-2
Hypersensitivity, Immediate
Interleukin-5
Antigen-Presenting Cells
Cell Line
Female
T-Lymphocyte Subsets
Cell Adhesion

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Larché, M., Till, S. J., Haselden, B. M., North, J., Barkans, J., Corrigan, C. J., Kay, A. B., & Robinson, D. S. (1998). Costimulation through CD86 is involved in airway antigen-presenting cell and T cell responses to allergen in atopic asthmatics. Journal of Immunology, 161(11), 6375-82. http://www.google.co.uk/url?sa=t&rct=j&q=&esrc=s&source=web&cd=2&ved=0ahUKEwjd64eM2JHPAhVbFMAKHcjqBD0QFggkMAE&url=http%3A%2F%2Fwww.jimmunol.org%2Fcontent%2F161%2F11%2F6375.full.pdf&usg=AFQjCNGpjD2nehEp0TZf5q5gdEQkWVkLWw

@article{3f3a6f60691b48d5a32ef4fc5a920f1d,

title = "Costimulation through CD86 is involved in airway antigen-presenting cell and T cell responses to allergen in atopic asthmatics",

abstract = "Atopic allergic asthma is characterized by activation of Th2-type T cells in the bronchial mucosa. Previous reports have suggested an important role for costimulation through the CD28/CTLA4-CD80/CD86 pathway in allergen activation of T cells in animal models of inhaled allergen challenge. However, human allergen-specific lines and clones were reported to be costimulation independent. We therefore examined CD80 and CD86 dependence of allergen-induced T cell proliferation and cytokine production in peripheral blood and bronchoalveolar lavage from atopic asthmatic subjects and controls. Both allergen-induced proliferation and IL-5 production from PBMC were inhibited by CTLA4-Ig fusion protein and anti-CD86, but not anti-CD80 mAbs. When allergen-specific CD4+ T cell lines from peripheral blood were examined, proliferation and cytokine production were found to be independent of CD80 or CD86 costimulation. However, when cells obtained directly from the airways were examined, allergen-induced proliferation of bronchoalveolar lavage T cells from atopic asthmatic subjects was inhibited by anti-CD86 but not anti-CD80. In addition, bronchoalveolar lavage-adherent cells from asthmatic, but not control subjects showed APC activity to autologous T cells. This was also inhibited by anti-CD86 but not anti-CD80. Thus allergen-induced T cell activation and IL-5 production in the airway in asthmatic subjects is susceptible to blockade by agents interfering with costimulation via CD86, and this may hold therapeutic potential in asthma.",

keywords = "Antigens, Differentiation, Membrane Glycoproteins, Humans, Antigens, CD45, Lymphocyte Activation, Antibodies, Monoclonal, Antigens, CD, Allergens, Bronchoalveolar Lavage Fluid, Adult, Cytokines, Male, Immunoconjugates, Antigen Presentation, Leukocytes, Mononuclear, Asthma, Antigens, CD86, Immunosuppressive Agents, CD4-Positive T-Lymphocytes, CTLA-4 Antigen, Bronchi, Interleukin-2, Hypersensitivity, Immediate, Interleukin-5, Antigen-Presenting Cells, Cell Line, Female, T-Lymphocyte Subsets, Cell Adhesion",

author = "M Larch{\'e} and Till, {S J} and Haselden, {B M} and J North and J Barkans and Corrigan, {C J} and Kay, {A B} and Robinson, {D S}",

year = "1998",

month = dec,

day = "1",

language = "English",

volume = "161",

pages = "6375--82",

journal = "Journal of Immunology",

issn = "0022-1767",

publisher = "American Association of Immunologists",

number = "11",

}

Larché, M, Till, SJ, Haselden, BM, North, J, Barkans, J, Corrigan, CJ , Kay, AB & Robinson, DS 1998, 'Costimulation through CD86 is involved in airway antigen-presenting cell and T cell responses to allergen in atopic asthmatics', Journal of Immunology, vol. 161, no. 11, pp. 6375-82. <http://www.google.co.uk/url?sa=t&rct=j&q=&esrc=s&source=web&cd=2&ved=0ahUKEwjd64eM2JHPAhVbFMAKHcjqBD0QFggkMAE&url=http%3A%2F%2Fwww.jimmunol.org%2Fcontent%2F161%2F11%2F6375.full.pdf&usg=AFQjCNGpjD2nehEp0TZf5q5gdEQkWVkLWw>

TY - JOUR

T1 - Costimulation through CD86 is involved in airway antigen-presenting cell and T cell responses to allergen in atopic asthmatics

AU - Larché, M

AU - Till, S J

AU - Haselden, B M

AU - North, J

AU - Barkans, J

AU - Corrigan, C J

AU - Kay, A B

AU - Robinson, D S

PY - 1998/12/1

Y1 - 1998/12/1

N2 - Atopic allergic asthma is characterized by activation of Th2-type T cells in the bronchial mucosa. Previous reports have suggested an important role for costimulation through the CD28/CTLA4-CD80/CD86 pathway in allergen activation of T cells in animal models of inhaled allergen challenge. However, human allergen-specific lines and clones were reported to be costimulation independent. We therefore examined CD80 and CD86 dependence of allergen-induced T cell proliferation and cytokine production in peripheral blood and bronchoalveolar lavage from atopic asthmatic subjects and controls. Both allergen-induced proliferation and IL-5 production from PBMC were inhibited by CTLA4-Ig fusion protein and anti-CD86, but not anti-CD80 mAbs. When allergen-specific CD4+ T cell lines from peripheral blood were examined, proliferation and cytokine production were found to be independent of CD80 or CD86 costimulation. However, when cells obtained directly from the airways were examined, allergen-induced proliferation of bronchoalveolar lavage T cells from atopic asthmatic subjects was inhibited by anti-CD86 but not anti-CD80. In addition, bronchoalveolar lavage-adherent cells from asthmatic, but not control subjects showed APC activity to autologous T cells. This was also inhibited by anti-CD86 but not anti-CD80. Thus allergen-induced T cell activation and IL-5 production in the airway in asthmatic subjects is susceptible to blockade by agents interfering with costimulation via CD86, and this may hold therapeutic potential in asthma.

AB - Atopic allergic asthma is characterized by activation of Th2-type T cells in the bronchial mucosa. Previous reports have suggested an important role for costimulation through the CD28/CTLA4-CD80/CD86 pathway in allergen activation of T cells in animal models of inhaled allergen challenge. However, human allergen-specific lines and clones were reported to be costimulation independent. We therefore examined CD80 and CD86 dependence of allergen-induced T cell proliferation and cytokine production in peripheral blood and bronchoalveolar lavage from atopic asthmatic subjects and controls. Both allergen-induced proliferation and IL-5 production from PBMC were inhibited by CTLA4-Ig fusion protein and anti-CD86, but not anti-CD80 mAbs. When allergen-specific CD4+ T cell lines from peripheral blood were examined, proliferation and cytokine production were found to be independent of CD80 or CD86 costimulation. However, when cells obtained directly from the airways were examined, allergen-induced proliferation of bronchoalveolar lavage T cells from atopic asthmatic subjects was inhibited by anti-CD86 but not anti-CD80. In addition, bronchoalveolar lavage-adherent cells from asthmatic, but not control subjects showed APC activity to autologous T cells. This was also inhibited by anti-CD86 but not anti-CD80. Thus allergen-induced T cell activation and IL-5 production in the airway in asthmatic subjects is susceptible to blockade by agents interfering with costimulation via CD86, and this may hold therapeutic potential in asthma.

KW - Antigens, Differentiation

KW - Membrane Glycoproteins

KW - Humans

KW - Antigens, CD45

KW - Lymphocyte Activation

KW - Antibodies, Monoclonal

KW - Antigens, CD

KW - Allergens

KW - Bronchoalveolar Lavage Fluid

KW - Adult

KW - Cytokines

KW - Male

KW - Immunoconjugates

KW - Antigen Presentation

KW - Leukocytes, Mononuclear

KW - Asthma

KW - Antigens, CD86

KW - Immunosuppressive Agents

KW - CD4-Positive T-Lymphocytes

KW - CTLA-4 Antigen

KW - Bronchi

KW - Interleukin-2

KW - Hypersensitivity, Immediate

KW - Interleukin-5

KW - Antigen-Presenting Cells

KW - Cell Line

KW - Female

KW - T-Lymphocyte Subsets

KW - Cell Adhesion

M3 - Article

C2 - 9834128

SN - 0022-1767

VL - 161

SP - 6375

EP - 6382

JO - Journal of Immunology

JF - Journal of Immunology

IS - 11

ER -

Costimulation through CD86 is involved in airway antigen-presenting cell and T cell responses to allergen in atopic asthmatics

Abstract

Keywords

UN SDGs

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