Selective Induction of Dendritic Cells Using Granulocyte Macrophage-Colony Stimulating Factor, But Not fms-Like Tyrosine Kinase Receptor 3-Ligand, Activates Thyroglobulin-Specific CD4+/CD25+ T Cells and Suppresses Experimental Autoimmune Thyroiditis

Fms-like tyrosine kinase receptor 3-ligand (Flt3-L) and GM-CSF cause expansion of different subsets of dendritic cells and skew the immune response toward predominantly Th1 and Th2 type, respectively. In the present study, we investigated their effects on experimental autoimmune thyroiditis in CBA/J...

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Veröffentlicht in:The Journal of immunology (1950) 2003-06, Vol.170 (11), p.5511-5522
Hauptverfasser: Vasu, Chenthamarakshan, Dogan, Rukiye-Nazan E, Holterman, Mark J, Prabhakar, Bellur S
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container_issue 11
container_start_page 5511
container_title The Journal of immunology (1950)
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creator Vasu, Chenthamarakshan
Dogan, Rukiye-Nazan E
Holterman, Mark J
Prabhakar, Bellur S
description Fms-like tyrosine kinase receptor 3-ligand (Flt3-L) and GM-CSF cause expansion of different subsets of dendritic cells and skew the immune response toward predominantly Th1 and Th2 type, respectively. In the present study, we investigated their effects on experimental autoimmune thyroiditis in CBA/J mice. Relative to mouse thyroglobulin (mTg) immunized controls, mTg-immunized mice treated with Flt3-L showed more severe thyroiditis characterized by enhanced lymphocytic infiltration of the thyroid, and IFN-gamma and IL-2 production. In contrast, mice treated with GM-CSF, either before or after immunization with mTg, showed suppressed T cell response to mTg and failed to develop thyroiditis. Lymphocytes from these mice, upon activation with mTg in vitro, produced higher levels of IL-4 and IL-10. Additionally, GM-CSF-treated mice showed an increase in the frequency of CD4(+)/CD25(+) T cells, which suppressed the mTg-specific T cell response. Neutralization of IL-10, but not IL-4, or depletion of CD4(+)/CD25(+) cells resulted in increased mTg-specific in vitro T cell proliferation suggesting that IL-10 produced by the Ag-specific CD4(+)/CD25(+) regulatory T cells might be critical for disease suppression. These results indicate that skewing immune response toward Th2, through selective activation of dendritic cells using GM-CSF, may have therapeutic potential in Th1 dominant autoimmune diseases including Hashimoto's thyroiditis.
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In the present study, we investigated their effects on experimental autoimmune thyroiditis in CBA/J mice. Relative to mouse thyroglobulin (mTg) immunized controls, mTg-immunized mice treated with Flt3-L showed more severe thyroiditis characterized by enhanced lymphocytic infiltration of the thyroid, and IFN-gamma and IL-2 production. In contrast, mice treated with GM-CSF, either before or after immunization with mTg, showed suppressed T cell response to mTg and failed to develop thyroiditis. Lymphocytes from these mice, upon activation with mTg in vitro, produced higher levels of IL-4 and IL-10. Additionally, GM-CSF-treated mice showed an increase in the frequency of CD4(+)/CD25(+) T cells, which suppressed the mTg-specific T cell response. Neutralization of IL-10, but not IL-4, or depletion of CD4(+)/CD25(+) cells resulted in increased mTg-specific in vitro T cell proliferation suggesting that IL-10 produced by the Ag-specific CD4(+)/CD25(+) regulatory T cells might be critical for disease suppression. 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In the present study, we investigated their effects on experimental autoimmune thyroiditis in CBA/J mice. Relative to mouse thyroglobulin (mTg) immunized controls, mTg-immunized mice treated with Flt3-L showed more severe thyroiditis characterized by enhanced lymphocytic infiltration of the thyroid, and IFN-gamma and IL-2 production. In contrast, mice treated with GM-CSF, either before or after immunization with mTg, showed suppressed T cell response to mTg and failed to develop thyroiditis. Lymphocytes from these mice, upon activation with mTg in vitro, produced higher levels of IL-4 and IL-10. Additionally, GM-CSF-treated mice showed an increase in the frequency of CD4(+)/CD25(+) T cells, which suppressed the mTg-specific T cell response. Neutralization of IL-10, but not IL-4, or depletion of CD4(+)/CD25(+) cells resulted in increased mTg-specific in vitro T cell proliferation suggesting that IL-10 produced by the Ag-specific CD4(+)/CD25(+) regulatory T cells might be critical for disease suppression. These results indicate that skewing immune response toward Th2, through selective activation of dendritic cells using GM-CSF, may have therapeutic potential in Th1 dominant autoimmune diseases including Hashimoto's thyroiditis.</description><subject>Animals</subject><subject>Autoantibodies - biosynthesis</subject><subject>CD4-Positive T-Lymphocytes - immunology</subject><subject>CD4-Positive T-Lymphocytes - metabolism</subject><subject>CD4-Positive T-Lymphocytes - pathology</subject><subject>Cell Division - immunology</subject><subject>Cytokines - antagonists &amp; inhibitors</subject><subject>Cytokines - biosynthesis</subject><subject>Dendritic Cells - classification</subject><subject>Dendritic Cells - immunology</subject><subject>Dendritic Cells - metabolism</subject><subject>Down-Regulation - immunology</subject><subject>Epitopes, T-Lymphocyte - immunology</subject><subject>Female</subject><subject>Granulocyte-Macrophage Colony-Stimulating Factor - pharmacology</subject><subject>Growth Inhibitors - pharmacology</subject><subject>Humans</subject><subject>Interleukin-10 - physiology</subject><subject>Interleukin-4 - physiology</subject><subject>Lymphocyte Activation - drug effects</subject><subject>Lymphocyte Activation - immunology</subject><subject>Membrane Proteins - pharmacology</subject><subject>Mice</subject><subject>Mice, Inbred CBA</subject><subject>Receptor Protein-Tyrosine Kinases - metabolism</subject><subject>Receptors, Interleukin-2 - biosynthesis</subject><subject>Recombinant Proteins</subject><subject>Severity of Illness Index</subject><subject>T-Lymphocyte Subsets - immunology</subject><subject>T-Lymphocyte Subsets - metabolism</subject><subject>T-Lymphocyte Subsets - pathology</subject><subject>Thyroglobulin - immunology</subject><subject>Thyroglobulin - pharmacology</subject><subject>Thyroiditis, Autoimmune - immunology</subject><subject>Thyroiditis, Autoimmune - pathology</subject><subject>Thyroiditis, Autoimmune - prevention &amp; 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control</topic><topic>Up-Regulation - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Vasu, Chenthamarakshan</creatorcontrib><creatorcontrib>Dogan, Rukiye-Nazan E</creatorcontrib><creatorcontrib>Holterman, Mark J</creatorcontrib><creatorcontrib>Prabhakar, Bellur S</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>The Journal of immunology (1950)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Vasu, Chenthamarakshan</au><au>Dogan, Rukiye-Nazan E</au><au>Holterman, Mark J</au><au>Prabhakar, Bellur S</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Selective Induction of Dendritic Cells Using Granulocyte Macrophage-Colony Stimulating Factor, But Not fms-Like Tyrosine Kinase Receptor 3-Ligand, Activates Thyroglobulin-Specific CD4+/CD25+ T Cells and Suppresses Experimental Autoimmune Thyroiditis</atitle><jtitle>The Journal of immunology (1950)</jtitle><addtitle>J Immunol</addtitle><date>2003-06-01</date><risdate>2003</risdate><volume>170</volume><issue>11</issue><spage>5511</spage><epage>5522</epage><pages>5511-5522</pages><issn>0022-1767</issn><eissn>1550-6606</eissn><abstract>Fms-like tyrosine kinase receptor 3-ligand (Flt3-L) and GM-CSF cause expansion of different subsets of dendritic cells and skew the immune response toward predominantly Th1 and Th2 type, respectively. 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Neutralization of IL-10, but not IL-4, or depletion of CD4(+)/CD25(+) cells resulted in increased mTg-specific in vitro T cell proliferation suggesting that IL-10 produced by the Ag-specific CD4(+)/CD25(+) regulatory T cells might be critical for disease suppression. These results indicate that skewing immune response toward Th2, through selective activation of dendritic cells using GM-CSF, may have therapeutic potential in Th1 dominant autoimmune diseases including Hashimoto's thyroiditis.</abstract><cop>United States</cop><pub>Am Assoc Immnol</pub><pmid>12759428</pmid><doi>10.4049/jimmunol.170.11.5511</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record>
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subjects Animals
Autoantibodies - biosynthesis
CD4-Positive T-Lymphocytes - immunology
CD4-Positive T-Lymphocytes - metabolism
CD4-Positive T-Lymphocytes - pathology
Cell Division - immunology
Cytokines - antagonists & inhibitors
Cytokines - biosynthesis
Dendritic Cells - classification
Dendritic Cells - immunology
Dendritic Cells - metabolism
Down-Regulation - immunology
Epitopes, T-Lymphocyte - immunology
Female
Granulocyte-Macrophage Colony-Stimulating Factor - pharmacology
Growth Inhibitors - pharmacology
Humans
Interleukin-10 - physiology
Interleukin-4 - physiology
Lymphocyte Activation - drug effects
Lymphocyte Activation - immunology
Membrane Proteins - pharmacology
Mice
Mice, Inbred CBA
Receptor Protein-Tyrosine Kinases - metabolism
Receptors, Interleukin-2 - biosynthesis
Recombinant Proteins
Severity of Illness Index
T-Lymphocyte Subsets - immunology
T-Lymphocyte Subsets - metabolism
T-Lymphocyte Subsets - pathology
Thyroglobulin - immunology
Thyroglobulin - pharmacology
Thyroiditis, Autoimmune - immunology
Thyroiditis, Autoimmune - pathology
Thyroiditis, Autoimmune - prevention & control
Up-Regulation - immunology
title Selective Induction of Dendritic Cells Using Granulocyte Macrophage-Colony Stimulating Factor, But Not fms-Like Tyrosine Kinase Receptor 3-Ligand, Activates Thyroglobulin-Specific CD4+/CD25+ T Cells and Suppresses Experimental Autoimmune Thyroiditis
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