Allergic inflammatory response to short ragweed allergenic extract in HLA-DQ transgenic mice lacking CD4 gene

S. P. Chapoval, K. Iijima, E. V. Marietta, M. K. Smart, Andrei Chapoval, A. G. Andrews, C. S. David

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

To investigate the role of HLA-DQ molecules and/or CD4+ T cells in the pathogenesis of allergic asthma, we generated HLA-DQ6 and HLA-DQ8 transgenic mice lacking endogenous class II (Aβnull) and CD4 genes and challenged them intranasally with short ragweed allergenic extract (SRW). We found that DQ6/CD4null mice developed a strong eosinophilic infiltration into the bronchoalveolar lavage and lung tissue, while DQ8/CD4null mice were normal. However, neither cytokines nor eosinophil peroxidase in the bronchoalveolar lavage of DQ6/CD4null mice was found. In addition, the airway reactivity to methacholine was elevated moderately in DQ6/CD4null mice compared with the high response in DQ/CD4+ counterparts and was only partially augmented by CD4+ T cell transfer. The DQ6/CD4null mice showed Th1/Th2-type cytokines and SRW-specific Abs in the immune sera in contrast to a direct Th2 response observed in DQ6/CD4+ mice. The proliferative response of spleen mononuclear cells and peribronchial lymph node cells demonstrated that the response to SRW in DQ6/CD4null mice was mediated by HLA-DQ-restricted CD4-CD8-NK1.1- T cells. FA CS analysis of PBMC and spleen mononuclear cells demonstrated an expansion of double-negative (DN) CD4-CD8-TCRαβ+ T cells in SRW-treated DQ6/CD4null mice. These cells produced IL-4, IL-5, IL-13, and IFN-γ, when stimulated with immobilized anti-CD3. IL-5 ELISPOT assay revealed that DN T cells were the cellular origin of IL-5 in allergen-challenged DQ6/CD4null mice. Our study shows a role for HLA-DQ-restricted CD4+ and DN T cells in the allergic response.

Original languageEnglish (US)
Pages (from-to)890-899
Number of pages10
JournalJournal of Immunology
Volume168
Issue number2
DOIs
StatePublished - Jan 15 2002
Externally publishedYes

Fingerprint

HLA-DQ Antigens
Ambrosia
Transgenic Mice
Genes
T-Lymphocytes
Interleukin-5
Bronchoalveolar Lavage
Spleen
Eosinophil Peroxidase
Cytokines
Enzyme-Linked Immunospot Assay
CD4 Antigens
Interleukin-13
Methacholine Chloride
Interleukin-4
Allergens
Immune Sera
Asthma
Lymph Nodes
Lung

ASJC Scopus subject areas

  • Immunology

Cite this

Allergic inflammatory response to short ragweed allergenic extract in HLA-DQ transgenic mice lacking CD4 gene. / Chapoval, S. P.; Iijima, K.; Marietta, E. V.; Smart, M. K.; Chapoval, Andrei; Andrews, A. G.; David, C. S.

In: Journal of Immunology, Vol. 168, No. 2, 15.01.2002, p. 890-899.

Research output: Contribution to journalArticle

Chapoval, S. P. ; Iijima, K. ; Marietta, E. V. ; Smart, M. K. ; Chapoval, Andrei ; Andrews, A. G. ; David, C. S. / Allergic inflammatory response to short ragweed allergenic extract in HLA-DQ transgenic mice lacking CD4 gene. In: Journal of Immunology. 2002 ; Vol. 168, No. 2. pp. 890-899.
@article{4a382cc017574f77a5f5f2fd7d8aa8e0,
title = "Allergic inflammatory response to short ragweed allergenic extract in HLA-DQ transgenic mice lacking CD4 gene",
abstract = "To investigate the role of HLA-DQ molecules and/or CD4+ T cells in the pathogenesis of allergic asthma, we generated HLA-DQ6 and HLA-DQ8 transgenic mice lacking endogenous class II (Aβnull) and CD4 genes and challenged them intranasally with short ragweed allergenic extract (SRW). We found that DQ6/CD4null mice developed a strong eosinophilic infiltration into the bronchoalveolar lavage and lung tissue, while DQ8/CD4null mice were normal. However, neither cytokines nor eosinophil peroxidase in the bronchoalveolar lavage of DQ6/CD4null mice was found. In addition, the airway reactivity to methacholine was elevated moderately in DQ6/CD4null mice compared with the high response in DQ/CD4+ counterparts and was only partially augmented by CD4+ T cell transfer. The DQ6/CD4null mice showed Th1/Th2-type cytokines and SRW-specific Abs in the immune sera in contrast to a direct Th2 response observed in DQ6/CD4+ mice. The proliferative response of spleen mononuclear cells and peribronchial lymph node cells demonstrated that the response to SRW in DQ6/CD4null mice was mediated by HLA-DQ-restricted CD4-CD8-NK1.1- T cells. FA CS analysis of PBMC and spleen mononuclear cells demonstrated an expansion of double-negative (DN) CD4-CD8-TCRαβ+ T cells in SRW-treated DQ6/CD4null mice. These cells produced IL-4, IL-5, IL-13, and IFN-γ, when stimulated with immobilized anti-CD3. IL-5 ELISPOT assay revealed that DN T cells were the cellular origin of IL-5 in allergen-challenged DQ6/CD4null mice. Our study shows a role for HLA-DQ-restricted CD4+ and DN T cells in the allergic response.",
author = "Chapoval, {S. P.} and K. Iijima and Marietta, {E. V.} and Smart, {M. K.} and Andrei Chapoval and Andrews, {A. G.} and David, {C. S.}",
year = "2002",
month = "1",
day = "15",
doi = "10.4049/jimmunol.168.2.890",
language = "English (US)",
volume = "168",
pages = "890--899",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "2",

}

TY - JOUR

T1 - Allergic inflammatory response to short ragweed allergenic extract in HLA-DQ transgenic mice lacking CD4 gene

AU - Chapoval, S. P.

AU - Iijima, K.

AU - Marietta, E. V.

AU - Smart, M. K.

AU - Chapoval, Andrei

AU - Andrews, A. G.

AU - David, C. S.

PY - 2002/1/15

Y1 - 2002/1/15

N2 - To investigate the role of HLA-DQ molecules and/or CD4+ T cells in the pathogenesis of allergic asthma, we generated HLA-DQ6 and HLA-DQ8 transgenic mice lacking endogenous class II (Aβnull) and CD4 genes and challenged them intranasally with short ragweed allergenic extract (SRW). We found that DQ6/CD4null mice developed a strong eosinophilic infiltration into the bronchoalveolar lavage and lung tissue, while DQ8/CD4null mice were normal. However, neither cytokines nor eosinophil peroxidase in the bronchoalveolar lavage of DQ6/CD4null mice was found. In addition, the airway reactivity to methacholine was elevated moderately in DQ6/CD4null mice compared with the high response in DQ/CD4+ counterparts and was only partially augmented by CD4+ T cell transfer. The DQ6/CD4null mice showed Th1/Th2-type cytokines and SRW-specific Abs in the immune sera in contrast to a direct Th2 response observed in DQ6/CD4+ mice. The proliferative response of spleen mononuclear cells and peribronchial lymph node cells demonstrated that the response to SRW in DQ6/CD4null mice was mediated by HLA-DQ-restricted CD4-CD8-NK1.1- T cells. FA CS analysis of PBMC and spleen mononuclear cells demonstrated an expansion of double-negative (DN) CD4-CD8-TCRαβ+ T cells in SRW-treated DQ6/CD4null mice. These cells produced IL-4, IL-5, IL-13, and IFN-γ, when stimulated with immobilized anti-CD3. IL-5 ELISPOT assay revealed that DN T cells were the cellular origin of IL-5 in allergen-challenged DQ6/CD4null mice. Our study shows a role for HLA-DQ-restricted CD4+ and DN T cells in the allergic response.

AB - To investigate the role of HLA-DQ molecules and/or CD4+ T cells in the pathogenesis of allergic asthma, we generated HLA-DQ6 and HLA-DQ8 transgenic mice lacking endogenous class II (Aβnull) and CD4 genes and challenged them intranasally with short ragweed allergenic extract (SRW). We found that DQ6/CD4null mice developed a strong eosinophilic infiltration into the bronchoalveolar lavage and lung tissue, while DQ8/CD4null mice were normal. However, neither cytokines nor eosinophil peroxidase in the bronchoalveolar lavage of DQ6/CD4null mice was found. In addition, the airway reactivity to methacholine was elevated moderately in DQ6/CD4null mice compared with the high response in DQ/CD4+ counterparts and was only partially augmented by CD4+ T cell transfer. The DQ6/CD4null mice showed Th1/Th2-type cytokines and SRW-specific Abs in the immune sera in contrast to a direct Th2 response observed in DQ6/CD4+ mice. The proliferative response of spleen mononuclear cells and peribronchial lymph node cells demonstrated that the response to SRW in DQ6/CD4null mice was mediated by HLA-DQ-restricted CD4-CD8-NK1.1- T cells. FA CS analysis of PBMC and spleen mononuclear cells demonstrated an expansion of double-negative (DN) CD4-CD8-TCRαβ+ T cells in SRW-treated DQ6/CD4null mice. These cells produced IL-4, IL-5, IL-13, and IFN-γ, when stimulated with immobilized anti-CD3. IL-5 ELISPOT assay revealed that DN T cells were the cellular origin of IL-5 in allergen-challenged DQ6/CD4null mice. Our study shows a role for HLA-DQ-restricted CD4+ and DN T cells in the allergic response.

UR - http://www.scopus.com/inward/record.url?scp=0037080361&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037080361&partnerID=8YFLogxK

U2 - 10.4049/jimmunol.168.2.890

DO - 10.4049/jimmunol.168.2.890

M3 - Article

C2 - 11777987

AN - SCOPUS:0037080361

VL - 168

SP - 890

EP - 899

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 2

ER -