Aluminium hydroxide down-regulates T helper 2 responses by allergen-stimulated human peripheral blood mononuclear cells

L K Wilcock; J N Francis; S R Durham

doi:10.1111/j.1365-2222.2004.02052.x

Aluminium hydroxide down-regulates T helper 2 responses by allergen-stimulated human peripheral blood mononuclear cells

L K Wilcock, J N Francis, S R Durham

Randall Centre of Cell & Molecular Biophysics

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

48 Citations (Scopus)

Abstract

BACKGROUND: Aluminium hydroxide (alum) is a commonly used adjuvant for specific immunotherapy of allergic diseases. While alum is traditionally associated with murine Th2 sensitization, little is known about its effects on secondary allergic responses in humans.

METHODS: We investigated the in vitro effects of alum on peripheral blood mononuclear cells (PBMC) from atopic donors. PBMC from 18 grass pollen-sensitive rhinitic subjects were stimulated with Phleum pratense (Phl p) in the presence or absence of alum. After 6 days culture, cytokine production was measured by ELISA and T cell proliferation by radiolabelled thymidine incorporation. The effect of alum on the expression of human leucocyte antigen and CD80/CD86 on cultured antigen-presenting cells was assessed by flow cytometry.

RESULTS: PBMC cultured with Phl p and alum showed a significant decrease in both IL-5 and IL-13 production compared with allergen alone (P<0.005 and P<0.001, respectively), but no change in IFN-gamma or IL-12 production or proliferative responses. These alum-induced changes in T helper (Th)2 cytokine production were unaffected by the addition of neutralizing antibodies to IL-4 or IL-12. Culture of PBMC with alum induced increased expression of CD86 (P=0.004) and HLA (P=0.01) on monocytes while the expression of CD80 was decreased (P=0.02).

SUMMARY: Alum down-regulates allergen-driven Th2 cytokine responses while Th1 cytokines are unaffected. These data confirm that alum is a useful adjuvant for inclusion in allergen immunotherapy vaccines.

Original language	English
Pages (from-to)	1373-1378
Number of pages	6
Journal	Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology
Volume	34
Issue number	9
DOIs	https://doi.org/10.1111/j.1365-2222.2004.02052.x
Publication status	Published - 3 Sept 2004

Keywords

Adjuvants, Immunologic
Adult
Allergens
Aluminum Hydroxide
Antigen-Presenting Cells
Antigens, CD
Antigens, CD80
Antigens, CD86
Cells, Cultured
Down-Regulation
Female
HLA Antigens
Humans
Interferon-gamma
Interleukin-12
Interleukin-13
Interleukin-4
Interleukin-5
Leukocytes, Mononuclear
Male
Membrane Glycoproteins
Phleum
Pollen
Rhinitis, Allergic, Seasonal
Th2 Cells

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10.1111/j.1365-2222.2004.02052.x

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title = "Aluminium hydroxide down-regulates T helper 2 responses by allergen-stimulated human peripheral blood mononuclear cells",

abstract = "BACKGROUND: Aluminium hydroxide (alum) is a commonly used adjuvant for specific immunotherapy of allergic diseases. While alum is traditionally associated with murine Th2 sensitization, little is known about its effects on secondary allergic responses in humans.METHODS: We investigated the in vitro effects of alum on peripheral blood mononuclear cells (PBMC) from atopic donors. PBMC from 18 grass pollen-sensitive rhinitic subjects were stimulated with Phleum pratense (Phl p) in the presence or absence of alum. After 6 days culture, cytokine production was measured by ELISA and T cell proliferation by radiolabelled thymidine incorporation. The effect of alum on the expression of human leucocyte antigen and CD80/CD86 on cultured antigen-presenting cells was assessed by flow cytometry.RESULTS: PBMC cultured with Phl p and alum showed a significant decrease in both IL-5 and IL-13 production compared with allergen alone (P<0.005 and P<0.001, respectively), but no change in IFN-gamma or IL-12 production or proliferative responses. These alum-induced changes in T helper (Th)2 cytokine production were unaffected by the addition of neutralizing antibodies to IL-4 or IL-12. Culture of PBMC with alum induced increased expression of CD86 (P=0.004) and HLA (P=0.01) on monocytes while the expression of CD80 was decreased (P=0.02).SUMMARY: Alum down-regulates allergen-driven Th2 cytokine responses while Th1 cytokines are unaffected. These data confirm that alum is a useful adjuvant for inclusion in allergen immunotherapy vaccines.",

keywords = "Adjuvants, Immunologic, Adult, Allergens, Aluminum Hydroxide, Antigen-Presenting Cells, Antigens, CD, Antigens, CD80, Antigens, CD86, Cells, Cultured, Down-Regulation, Female, HLA Antigens, Humans, Interferon-gamma, Interleukin-12, Interleukin-13, Interleukin-4, Interleukin-5, Leukocytes, Mononuclear, Male, Membrane Glycoproteins, Phleum, Pollen, Rhinitis, Allergic, Seasonal, Th2 Cells",

author = "Wilcock, {L K} and Francis, {J N} and Durham, {S R}",

year = "2004",

month = sep,

day = "3",

doi = "10.1111/j.1365-2222.2004.02052.x",

language = "English",

volume = "34",

pages = "1373--1378",

journal = "Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology",

issn = "0954-7894",

publisher = "Blackwell Publishing",

number = "9",

}

Aluminium hydroxide down-regulates T helper 2 responses by allergen-stimulated human peripheral blood mononuclear cells. / Wilcock, L K; Francis, J N; Durham, S R.
In: Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology, Vol. 34, No. 9, 03.09.2004, p. 1373-1378.

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

TY - JOUR

T1 - Aluminium hydroxide down-regulates T helper 2 responses by allergen-stimulated human peripheral blood mononuclear cells

AU - Wilcock, L K

AU - Francis, J N

AU - Durham, S R

PY - 2004/9/3

Y1 - 2004/9/3

N2 - BACKGROUND: Aluminium hydroxide (alum) is a commonly used adjuvant for specific immunotherapy of allergic diseases. While alum is traditionally associated with murine Th2 sensitization, little is known about its effects on secondary allergic responses in humans.METHODS: We investigated the in vitro effects of alum on peripheral blood mononuclear cells (PBMC) from atopic donors. PBMC from 18 grass pollen-sensitive rhinitic subjects were stimulated with Phleum pratense (Phl p) in the presence or absence of alum. After 6 days culture, cytokine production was measured by ELISA and T cell proliferation by radiolabelled thymidine incorporation. The effect of alum on the expression of human leucocyte antigen and CD80/CD86 on cultured antigen-presenting cells was assessed by flow cytometry.RESULTS: PBMC cultured with Phl p and alum showed a significant decrease in both IL-5 and IL-13 production compared with allergen alone (P<0.005 and P<0.001, respectively), but no change in IFN-gamma or IL-12 production or proliferative responses. These alum-induced changes in T helper (Th)2 cytokine production were unaffected by the addition of neutralizing antibodies to IL-4 or IL-12. Culture of PBMC with alum induced increased expression of CD86 (P=0.004) and HLA (P=0.01) on monocytes while the expression of CD80 was decreased (P=0.02).SUMMARY: Alum down-regulates allergen-driven Th2 cytokine responses while Th1 cytokines are unaffected. These data confirm that alum is a useful adjuvant for inclusion in allergen immunotherapy vaccines.

AB - BACKGROUND: Aluminium hydroxide (alum) is a commonly used adjuvant for specific immunotherapy of allergic diseases. While alum is traditionally associated with murine Th2 sensitization, little is known about its effects on secondary allergic responses in humans.METHODS: We investigated the in vitro effects of alum on peripheral blood mononuclear cells (PBMC) from atopic donors. PBMC from 18 grass pollen-sensitive rhinitic subjects were stimulated with Phleum pratense (Phl p) in the presence or absence of alum. After 6 days culture, cytokine production was measured by ELISA and T cell proliferation by radiolabelled thymidine incorporation. The effect of alum on the expression of human leucocyte antigen and CD80/CD86 on cultured antigen-presenting cells was assessed by flow cytometry.RESULTS: PBMC cultured with Phl p and alum showed a significant decrease in both IL-5 and IL-13 production compared with allergen alone (P<0.005 and P<0.001, respectively), but no change in IFN-gamma or IL-12 production or proliferative responses. These alum-induced changes in T helper (Th)2 cytokine production were unaffected by the addition of neutralizing antibodies to IL-4 or IL-12. Culture of PBMC with alum induced increased expression of CD86 (P=0.004) and HLA (P=0.01) on monocytes while the expression of CD80 was decreased (P=0.02).SUMMARY: Alum down-regulates allergen-driven Th2 cytokine responses while Th1 cytokines are unaffected. These data confirm that alum is a useful adjuvant for inclusion in allergen immunotherapy vaccines.

KW - Adjuvants, Immunologic

KW - Adult

KW - Allergens

KW - Aluminum Hydroxide

KW - Antigen-Presenting Cells

KW - Antigens, CD

KW - Antigens, CD80

KW - Antigens, CD86

KW - Cells, Cultured

KW - Down-Regulation

KW - Female

KW - HLA Antigens

KW - Humans

KW - Interferon-gamma

KW - Interleukin-12

KW - Interleukin-13

KW - Interleukin-4

KW - Interleukin-5

KW - Leukocytes, Mononuclear

KW - Male

KW - Membrane Glycoproteins

KW - Phleum

KW - Pollen

KW - Rhinitis, Allergic, Seasonal

KW - Th2 Cells

U2 - 10.1111/j.1365-2222.2004.02052.x

DO - 10.1111/j.1365-2222.2004.02052.x

M3 - Article

C2 - 15347369

SN - 0954-7894

VL - 34

SP - 1373

EP - 1378

JO - Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology

JF - Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology

IS - 9

ER -

Aluminium hydroxide down-regulates T helper 2 responses by allergen-stimulated human peripheral blood mononuclear cells

Abstract

Keywords

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