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In vivo mechanisms of acquired thymic tolerance.

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In vivo mechanisms of acquired thymic tolerance. / Chen, W; Issazadeh-Navikas, Shohreh; Sayegh, M H; Khoury, S J.

I: Cellular Immunology, Bind 179, Nr. 2, 1997, s. 165-73.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Harvard

Chen, W, Issazadeh-Navikas, S, Sayegh, MH & Khoury, SJ 1997, 'In vivo mechanisms of acquired thymic tolerance.', Cellular Immunology, bind 179, nr. 2, s. 165-73. https://doi.org/10.1006/cimm.1997.1165

APA

Chen, W., Issazadeh-Navikas, S., Sayegh, M. H., & Khoury, S. J. (1997). In vivo mechanisms of acquired thymic tolerance. Cellular Immunology, 179(2), 165-73. https://doi.org/10.1006/cimm.1997.1165

Vancouver

Chen W, Issazadeh-Navikas S, Sayegh MH, Khoury SJ. In vivo mechanisms of acquired thymic tolerance. Cellular Immunology. 1997;179(2):165-73. https://doi.org/10.1006/cimm.1997.1165

Author

Chen, W ; Issazadeh-Navikas, Shohreh ; Sayegh, M H ; Khoury, S J. / In vivo mechanisms of acquired thymic tolerance. I: Cellular Immunology. 1997 ; Bind 179, Nr. 2. s. 165-73.

Bibtex

@article{dbeb06d057d011dd8d9f000ea68e967b,
title = "In vivo mechanisms of acquired thymic tolerance.",
abstract = "Injection of antigen into the thymus of adult animals induces specific systemic tolerance, but the mechanisms of acquired thymic tolerance are not well understood. To investigate these mechanisms we used a model of intrathymic injection of ovalbumin (OVA) in BALB/c mice. We show an antigen-specific decrease in proliferative responses to OVA, as well as a significant decrease in antigen-specific IL-2 secretion and IFN-gamma production by splenocytes and lymph node cells of tolerant mice. Addition of recombinant IL-2 in vitro reversed the defect in IFN-gamma production by cells from OVA-tolerized animals, but did not reverse the proliferation or IL-2 production defects. By using an adoptive transfer system, where a small population of OVA peptide-specific CD4+ TCR transgenic T cells are transferred into syngeneic normal recipients, we show an absence of peripheral antigen-dependent clonal expansion of transferred CD4+ TCR transgenic cells in tolerant mice in vivo. There was an increase in clonotype-positive T cells in the thymus after immunization, confirming that activated T cells circulate through the thymus. Furthermore, thymectomy after intrathymic injection abrogates the effect of acquired thymic tolerance and restores antigen-dependent clonal expansion in vivo. We conclude that intrathymic injection of antigen induces Th1 cell unresponsiveness and prevents the peripheral expansion of antigen-specific CD4(+) T cells in vivo. This is the first demonstration that in acquired thymic tolerance antigen-specific T cells circulate to the thymus where they may be anergized or ultimately deleted.",
author = "W Chen and Shohreh Issazadeh-Navikas and Sayegh, {M H} and Khoury, {S J}",
note = "Keywords: Adoptive Transfer; Animals; CD4-Positive T-Lymphocytes; Cell Movement; Epitopes; Immune Tolerance; Injections, Intralymphatic; Interferon Type II; Interleukin-2; Kinetics; Lymphocyte Activation; Mice; Mice, Inbred BALB C; Mice, Transgenic; Ovalbumin; Receptors, Antigen, T-Cell; Recombinant Proteins; Th1 Cells; Thymectomy; Thymus Gland",
year = "1997",
doi = "10.1006/cimm.1997.1165",
language = "English",
volume = "179",
pages = "165--73",
journal = "Cellular Immunology",
issn = "0008-8749",
publisher = "Academic Press",
number = "2",

}

RIS

TY - JOUR

T1 - In vivo mechanisms of acquired thymic tolerance.

AU - Chen, W

AU - Issazadeh-Navikas, Shohreh

AU - Sayegh, M H

AU - Khoury, S J

N1 - Keywords: Adoptive Transfer; Animals; CD4-Positive T-Lymphocytes; Cell Movement; Epitopes; Immune Tolerance; Injections, Intralymphatic; Interferon Type II; Interleukin-2; Kinetics; Lymphocyte Activation; Mice; Mice, Inbred BALB C; Mice, Transgenic; Ovalbumin; Receptors, Antigen, T-Cell; Recombinant Proteins; Th1 Cells; Thymectomy; Thymus Gland

PY - 1997

Y1 - 1997

N2 - Injection of antigen into the thymus of adult animals induces specific systemic tolerance, but the mechanisms of acquired thymic tolerance are not well understood. To investigate these mechanisms we used a model of intrathymic injection of ovalbumin (OVA) in BALB/c mice. We show an antigen-specific decrease in proliferative responses to OVA, as well as a significant decrease in antigen-specific IL-2 secretion and IFN-gamma production by splenocytes and lymph node cells of tolerant mice. Addition of recombinant IL-2 in vitro reversed the defect in IFN-gamma production by cells from OVA-tolerized animals, but did not reverse the proliferation or IL-2 production defects. By using an adoptive transfer system, where a small population of OVA peptide-specific CD4+ TCR transgenic T cells are transferred into syngeneic normal recipients, we show an absence of peripheral antigen-dependent clonal expansion of transferred CD4+ TCR transgenic cells in tolerant mice in vivo. There was an increase in clonotype-positive T cells in the thymus after immunization, confirming that activated T cells circulate through the thymus. Furthermore, thymectomy after intrathymic injection abrogates the effect of acquired thymic tolerance and restores antigen-dependent clonal expansion in vivo. We conclude that intrathymic injection of antigen induces Th1 cell unresponsiveness and prevents the peripheral expansion of antigen-specific CD4(+) T cells in vivo. This is the first demonstration that in acquired thymic tolerance antigen-specific T cells circulate to the thymus where they may be anergized or ultimately deleted.

AB - Injection of antigen into the thymus of adult animals induces specific systemic tolerance, but the mechanisms of acquired thymic tolerance are not well understood. To investigate these mechanisms we used a model of intrathymic injection of ovalbumin (OVA) in BALB/c mice. We show an antigen-specific decrease in proliferative responses to OVA, as well as a significant decrease in antigen-specific IL-2 secretion and IFN-gamma production by splenocytes and lymph node cells of tolerant mice. Addition of recombinant IL-2 in vitro reversed the defect in IFN-gamma production by cells from OVA-tolerized animals, but did not reverse the proliferation or IL-2 production defects. By using an adoptive transfer system, where a small population of OVA peptide-specific CD4+ TCR transgenic T cells are transferred into syngeneic normal recipients, we show an absence of peripheral antigen-dependent clonal expansion of transferred CD4+ TCR transgenic cells in tolerant mice in vivo. There was an increase in clonotype-positive T cells in the thymus after immunization, confirming that activated T cells circulate through the thymus. Furthermore, thymectomy after intrathymic injection abrogates the effect of acquired thymic tolerance and restores antigen-dependent clonal expansion in vivo. We conclude that intrathymic injection of antigen induces Th1 cell unresponsiveness and prevents the peripheral expansion of antigen-specific CD4(+) T cells in vivo. This is the first demonstration that in acquired thymic tolerance antigen-specific T cells circulate to the thymus where they may be anergized or ultimately deleted.

U2 - 10.1006/cimm.1997.1165

DO - 10.1006/cimm.1997.1165

M3 - Journal article

C2 - 9268500

VL - 179

SP - 165

EP - 173

JO - Cellular Immunology

JF - Cellular Immunology

SN - 0008-8749

IS - 2

ER -

ID: 5122882