T cell Tolerance - Cellular and molecular features of immune regulation

Susanna Grundström

T cell Tolerance - Cellular and molecular features of immune regulation

Susanna Grundström

Forskningsoutput: Avhandling › Doktorsavhandling (sammanläggning)

Sammanfattning

Popular Abstract in Swedish
Olika toleransmekanismer kontrollerar immunsystemets aktivitet

Originalspråk	engelska
Kvalifikation	Doktor
Tilldelande institution
Handledare	[unknown], [unknown], handledare, Extern person
Tilldelningsdatum	2002 dec. 13
Förlag	Susanna Grundström, Box 724, 220 07 Lund.,
ISBN (tryckt)	91-628-5421-6
Status	Published - 2002

Bibliografisk information

Defence details

Date: 2002-12-13
Time: 13:00
Place: Rune Grubb-salen BMC, Sölvegatan 19, Lund.

External reviewer(s)

Name: Wraith, David C.
Title: Professor
Affiliation: Dept. of Pathology and Microbiology, University of Bristol, UK.

---

Article: I. Sundstedt A., Grundström S. and Dohlsten M. 1998. T cell- and perforin-dependent depletion of B cells in vivo by Staphylococcal enterotoxin A. Immunology. 95: 76-82.

Article: II. Grundström S., Dohlsten M. and Sundstedt A. 2000. IL-2 unresponsiveness in anergic CD4+ T cells is due to defective signaling through the common g-chain of the IL-2 receptor. J Immunol. 164: 1175-1184.

Article: III. Grundström S., Cederbom L., Sundstedt A., Scheipers P. and Ivars F. Superantigen-induced regulatory T cells display different suppressive functions in the presence or absence of natural regulatory CD4+CD25+ T cells in vivo. Submitted manuscript.

Article: IV. Grundström S., Anderson P., Scheipers P. and Sundstedt A. Defective transcription of the IL-2 gene is associated with impaired expression of NFkB in tolerant CD4+ T cells in vivo. Submitted manuscript.

Ämnesklassifikation (UKÄ)

Immunologi inom det medicinska området (Här ingår: Cell- och immunterapi)

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@phdthesis{6c76ef1361f641b99eb94cb54e6531d3,

title = "T cell Tolerance - Cellular and molecular features of immune regulation",

abstract = "The immune system has evolved regulatory mechanisms in order to balance the effects of deleterious immune responses. Such immunological tolerance may be specifically acquired by lymphocytes, although different cells of the immune system participate in the induction and maintenance of tolerance. This thesis work is based on investigations of different tolerance mechanisms induced in CD4+ T lymphocytes in vivo. T cell activation or tolerance has been experimentally induced in TCR-transgenic mice in order to study T cell tolerance both at the cellular and molecular level. The tolerant state of CD4+ T cells is characterised by deficient production of the growth factor IL-2 as well as a reduced proliferation. We have found that the activity of the transcription factor NFkB is altered in tolerant T cells and that this may contribute to the reduced expression of IL-2. Moreover, the ability of tolerant CD4+ T cells to respond to IL-2 is impaired and this is related to decreased activity of the JAK/STAT pathway downstream the IL-2 receptor. We have also shown that CD4+ T cells with regulatory functions may be induced after tolerance induction in vivo. These regulatory T cells down-modulate the expression of costimulatory molecules on APCs and suppress the activation of naive T cells in vitro. In contrast to CD4+ T cells, CD8+ T cells are less susceptible to tolerance induction and thus retain their cytotoxic capacity. These results contribute to the understanding of how immune tolerance is achieved.",

keywords = "transplantation, Immunologi, serologi, serology, Immunology, JAK/STAT., NFkB, suppression, IL-2, superantigen, T cells, tolerance",

author = "Susanna Grundstr{\"o}m",

note = "Defence details Date: 2002-12-13 Time: 13:00 Place: Rune Grubb-salen BMC, S{\"o}lvegatan 19, Lund. External reviewer(s) Name: Wraith, David C. Title: Professor Affiliation: Dept. of Pathology and Microbiology, University of Bristol, UK. --- Article: I. Sundstedt A., Grundstr{\"o}m S. and Dohlsten M. 1998. T cell- and perforin-dependent depletion of B cells in vivo by Staphylococcal enterotoxin A. Immunology. 95: 76-82. Article: II. Grundstr{\"o}m S., Dohlsten M. and Sundstedt A. 2000. IL-2 unresponsiveness in anergic CD4+ T cells is due to defective signaling through the common g-chain of the IL-2 receptor. J Immunol. 164: 1175-1184. Article: III. Grundstr{\"o}m S., Cederbom L., Sundstedt A., Scheipers P. and Ivars F. Superantigen-induced regulatory T cells display different suppressive functions in the presence or absence of natural regulatory CD4+CD25+ T cells in vivo. Submitted manuscript. Article: IV. Grundstr{\"o}m S., Anderson P., Scheipers P. and Sundstedt A. Defective transcription of the IL-2 gene is associated with impaired expression of NFkB in tolerant CD4+ T cells in vivo. Submitted manuscript.",

year = "2002",

language = "English",

isbn = "91-628-5421-6",

publisher = "Susanna Grundstr{\"o}m, Box 724, 220 07 Lund.,",

type = "Doctoral Thesis (compilation)",

}

TY - THES

T1 - T cell Tolerance - Cellular and molecular features of immune regulation

AU - Grundström, Susanna

N1 - Defence details Date: 2002-12-13 Time: 13:00 Place: Rune Grubb-salen BMC, Sölvegatan 19, Lund. External reviewer(s) Name: Wraith, David C. Title: Professor Affiliation: Dept. of Pathology and Microbiology, University of Bristol, UK. --- Article: I. Sundstedt A., Grundström S. and Dohlsten M. 1998. T cell- and perforin-dependent depletion of B cells in vivo by Staphylococcal enterotoxin A. Immunology. 95: 76-82. Article: II. Grundström S., Dohlsten M. and Sundstedt A. 2000. IL-2 unresponsiveness in anergic CD4+ T cells is due to defective signaling through the common g-chain of the IL-2 receptor. J Immunol. 164: 1175-1184. Article: III. Grundström S., Cederbom L., Sundstedt A., Scheipers P. and Ivars F. Superantigen-induced regulatory T cells display different suppressive functions in the presence or absence of natural regulatory CD4+CD25+ T cells in vivo. Submitted manuscript. Article: IV. Grundström S., Anderson P., Scheipers P. and Sundstedt A. Defective transcription of the IL-2 gene is associated with impaired expression of NFkB in tolerant CD4+ T cells in vivo. Submitted manuscript.

PY - 2002

Y1 - 2002

N2 - The immune system has evolved regulatory mechanisms in order to balance the effects of deleterious immune responses. Such immunological tolerance may be specifically acquired by lymphocytes, although different cells of the immune system participate in the induction and maintenance of tolerance. This thesis work is based on investigations of different tolerance mechanisms induced in CD4+ T lymphocytes in vivo. T cell activation or tolerance has been experimentally induced in TCR-transgenic mice in order to study T cell tolerance both at the cellular and molecular level. The tolerant state of CD4+ T cells is characterised by deficient production of the growth factor IL-2 as well as a reduced proliferation. We have found that the activity of the transcription factor NFkB is altered in tolerant T cells and that this may contribute to the reduced expression of IL-2. Moreover, the ability of tolerant CD4+ T cells to respond to IL-2 is impaired and this is related to decreased activity of the JAK/STAT pathway downstream the IL-2 receptor. We have also shown that CD4+ T cells with regulatory functions may be induced after tolerance induction in vivo. These regulatory T cells down-modulate the expression of costimulatory molecules on APCs and suppress the activation of naive T cells in vitro. In contrast to CD4+ T cells, CD8+ T cells are less susceptible to tolerance induction and thus retain their cytotoxic capacity. These results contribute to the understanding of how immune tolerance is achieved.

AB - The immune system has evolved regulatory mechanisms in order to balance the effects of deleterious immune responses. Such immunological tolerance may be specifically acquired by lymphocytes, although different cells of the immune system participate in the induction and maintenance of tolerance. This thesis work is based on investigations of different tolerance mechanisms induced in CD4+ T lymphocytes in vivo. T cell activation or tolerance has been experimentally induced in TCR-transgenic mice in order to study T cell tolerance both at the cellular and molecular level. The tolerant state of CD4+ T cells is characterised by deficient production of the growth factor IL-2 as well as a reduced proliferation. We have found that the activity of the transcription factor NFkB is altered in tolerant T cells and that this may contribute to the reduced expression of IL-2. Moreover, the ability of tolerant CD4+ T cells to respond to IL-2 is impaired and this is related to decreased activity of the JAK/STAT pathway downstream the IL-2 receptor. We have also shown that CD4+ T cells with regulatory functions may be induced after tolerance induction in vivo. These regulatory T cells down-modulate the expression of costimulatory molecules on APCs and suppress the activation of naive T cells in vitro. In contrast to CD4+ T cells, CD8+ T cells are less susceptible to tolerance induction and thus retain their cytotoxic capacity. These results contribute to the understanding of how immune tolerance is achieved.

KW - transplantation

KW - Immunologi

KW - serologi

KW - serology

KW - Immunology

KW - JAK/STAT.

KW - NFkB

KW - suppression

KW - IL-2

KW - superantigen

KW - T cells

KW - tolerance

M3 - Doctoral Thesis (compilation)

SN - 91-628-5421-6

PB - Susanna Grundström, Box 724, 220 07 Lund.,

ER -

T cell Tolerance - Cellular and molecular features of immune regulation

Sammanfattning

Bibliografisk information

Ämnesklassifikation (UKÄ)

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