Presence of 5E6+CD4+ T-lymphocytes in the allergen specific airway hyperresponsiveness murine model: New evidence of lymphocyte orchestration role

Justo A. Montalvo, A. Asea, Adam Wanner, J. Stein-Streilein

Research output: Contribution to journalArticle

Abstract

Purpose: This study is designed to describe the presence of a specific lineage of T lymphocytes, 5E6+CD4+, their cytokine expression and the potential implications in the pathogenesis of the airway inflammation in the airway hyperresponsiveness (AHR) murine model. Methods: Using the murine model of AHR to Ovalbumin(OVA), Balb/c mice, 8-12 weeks old were sensitized via skin painting and immunized with sequential intraperitoneal injections with 50 mg and 100 μg of OVA respectively, in soluble preparations on PBS. Two and three weeks after immunization the animals were challenged intranasally with 100μg of OVA. Lymphocytes presence in the lung, BAL fluid, spleen, and regional lymph nodes (peribronchial, cervical and inguinal) was characterized phenotypically via flow cytometry analysis. Subsequent characterization of the 5E6+CD4+ T lymphocytes was made via cytokine expression of specific mab, flow analysis and confocal microscopy. Results: 5E6+CD4+ T cells are a distinct subset of lymphocytes with large size and high scattered value. In the BAL cells there is marked increased of 5E6+CD4+ T cells (>500%) with the great majority of them expressing IL-4 (>90%) seen in the sensitized group over the control group, but not seen equivalently in the lung or spleen lymphocytes. This cytokine expression is seen as early as 2 hours post challenge in the sensitized animal. There is also a preferential increase in coexpression of both IL-4 and IL-5 in the peribronchial lymph node within these population (2 and 1.5 fold increase) not seen among inguinal lymph nodes. However, IFN-γ expression is only seen in the inguinal lymph nodes. The conventional CD4+ lymphocytes had minimal expression of these Th2 cytokine expression (i.e. similar as control group). Conclusion: A special T-lymphocyte linage active in the co-expression of Th2 cytokines is described in the OVA-induced AHR murine model. The early immune response observed in this particular NK-T cell suggests they have a pivotal role in the subsequent Th2 type cytokine response and the persistence of the airway inflammation. Clinical Implications: Therapeutic intervention to modulate the presence of 5E6+CD4+T lymphocytes and other inflammatory mediators involved in the persistence of bronchospasm may proven to be effective in a group asthmatic patients with this type of cells.

Original languageEnglish
JournalChest
Volume110
Issue number4 SUPPL.
StatePublished - Oct 1 1996

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Allergens
Lymphocytes
T-Lymphocytes
Ovalbumin
Cytokines
Groin
Lymph Nodes
Dimercaprol
Interleukin-4
Spleen
Inflammation
Bronchial Spasm
Lung
Control Groups
Paintings
Interleukin-5
Lymphocyte Subsets
Intraperitoneal Injections
Confocal Microscopy
Natural Killer Cells

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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Presence of 5E6+CD4+ T-lymphocytes in the allergen specific airway hyperresponsiveness murine model : New evidence of lymphocyte orchestration role. / Montalvo, Justo A.; Asea, A.; Wanner, Adam; Stein-Streilein, J.

In: Chest, Vol. 110, No. 4 SUPPL., 01.10.1996.

Research output: Contribution to journalArticle

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title = "Presence of 5E6+CD4+ T-lymphocytes in the allergen specific airway hyperresponsiveness murine model: New evidence of lymphocyte orchestration role",
abstract = "Purpose: This study is designed to describe the presence of a specific lineage of T lymphocytes, 5E6+CD4+, their cytokine expression and the potential implications in the pathogenesis of the airway inflammation in the airway hyperresponsiveness (AHR) murine model. Methods: Using the murine model of AHR to Ovalbumin(OVA), Balb/c mice, 8-12 weeks old were sensitized via skin painting and immunized with sequential intraperitoneal injections with 50 mg and 100 μg of OVA respectively, in soluble preparations on PBS. Two and three weeks after immunization the animals were challenged intranasally with 100μg of OVA. Lymphocytes presence in the lung, BAL fluid, spleen, and regional lymph nodes (peribronchial, cervical and inguinal) was characterized phenotypically via flow cytometry analysis. Subsequent characterization of the 5E6+CD4+ T lymphocytes was made via cytokine expression of specific mab, flow analysis and confocal microscopy. Results: 5E6+CD4+ T cells are a distinct subset of lymphocytes with large size and high scattered value. In the BAL cells there is marked increased of 5E6+CD4+ T cells (>500{\%}) with the great majority of them expressing IL-4 (>90{\%}) seen in the sensitized group over the control group, but not seen equivalently in the lung or spleen lymphocytes. This cytokine expression is seen as early as 2 hours post challenge in the sensitized animal. There is also a preferential increase in coexpression of both IL-4 and IL-5 in the peribronchial lymph node within these population (2 and 1.5 fold increase) not seen among inguinal lymph nodes. However, IFN-γ expression is only seen in the inguinal lymph nodes. The conventional CD4+ lymphocytes had minimal expression of these Th2 cytokine expression (i.e. similar as control group). Conclusion: A special T-lymphocyte linage active in the co-expression of Th2 cytokines is described in the OVA-induced AHR murine model. The early immune response observed in this particular NK-T cell suggests they have a pivotal role in the subsequent Th2 type cytokine response and the persistence of the airway inflammation. Clinical Implications: Therapeutic intervention to modulate the presence of 5E6+CD4+T lymphocytes and other inflammatory mediators involved in the persistence of bronchospasm may proven to be effective in a group asthmatic patients with this type of cells.",
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AU - Wanner, Adam

AU - Stein-Streilein, J.

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N2 - Purpose: This study is designed to describe the presence of a specific lineage of T lymphocytes, 5E6+CD4+, their cytokine expression and the potential implications in the pathogenesis of the airway inflammation in the airway hyperresponsiveness (AHR) murine model. Methods: Using the murine model of AHR to Ovalbumin(OVA), Balb/c mice, 8-12 weeks old were sensitized via skin painting and immunized with sequential intraperitoneal injections with 50 mg and 100 μg of OVA respectively, in soluble preparations on PBS. Two and three weeks after immunization the animals were challenged intranasally with 100μg of OVA. Lymphocytes presence in the lung, BAL fluid, spleen, and regional lymph nodes (peribronchial, cervical and inguinal) was characterized phenotypically via flow cytometry analysis. Subsequent characterization of the 5E6+CD4+ T lymphocytes was made via cytokine expression of specific mab, flow analysis and confocal microscopy. Results: 5E6+CD4+ T cells are a distinct subset of lymphocytes with large size and high scattered value. In the BAL cells there is marked increased of 5E6+CD4+ T cells (>500%) with the great majority of them expressing IL-4 (>90%) seen in the sensitized group over the control group, but not seen equivalently in the lung or spleen lymphocytes. This cytokine expression is seen as early as 2 hours post challenge in the sensitized animal. There is also a preferential increase in coexpression of both IL-4 and IL-5 in the peribronchial lymph node within these population (2 and 1.5 fold increase) not seen among inguinal lymph nodes. However, IFN-γ expression is only seen in the inguinal lymph nodes. The conventional CD4+ lymphocytes had minimal expression of these Th2 cytokine expression (i.e. similar as control group). Conclusion: A special T-lymphocyte linage active in the co-expression of Th2 cytokines is described in the OVA-induced AHR murine model. The early immune response observed in this particular NK-T cell suggests they have a pivotal role in the subsequent Th2 type cytokine response and the persistence of the airway inflammation. Clinical Implications: Therapeutic intervention to modulate the presence of 5E6+CD4+T lymphocytes and other inflammatory mediators involved in the persistence of bronchospasm may proven to be effective in a group asthmatic patients with this type of cells.

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