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T cell Tolerance - Cellular and molecular features of immune regulation

Grundström, Susanna LU (2002)
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... (More)
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. (Less)
Abstract (Swedish)
Popular Abstract in Swedish

Olika toleransmekanismer kontrollerar immunsystemets aktivitet
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author
supervisor
opponent
  • Professor Wraith, David C., Dept. of Pathology and Microbiology, University of Bristol, UK.
organization
publishing date
type
Thesis
publication status
published
subject
keywords
transplantation, Immunologi, serologi, serology, Immunology, JAK/STAT., NFkB, suppression, IL-2, superantigen, T cells, tolerance
pages
210 pages
publisher
Susanna Grundström, Box 724, 220 07 Lund.,
defense location
Rune Grubb-salen BMC, Sölvegatan 19, Lund.
defense date
2002-12-13 13:00:00
ISBN
91-628-5421-6
language
English
LU publication?
yes
additional info
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.
id
6c76ef13-61f6-41b9-9eb9-4cb54e6531d3 (old id 465202)
date added to LUP
2016-04-04 11:42:41
date last changed
2018-11-21 21:06:40
@phdthesis{6c76ef13-61f6-41b9-9eb9-4cb54e6531d3,
  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.},
  author       = {Grundström, Susanna},
  isbn         = {91-628-5421-6},
  language     = {eng},
  publisher    = {Susanna Grundström, Box 724, 220 07 Lund.,},
  school       = {Lund University},
  title        = {T cell Tolerance - Cellular and molecular features of immune regulation},
  year         = {2002},
}