IL-2 overcomes the unresponsiveness but fails to reverse the regulatory function of antigen-induced T regulatory cells
(2005) In Journal of Immunology 174(1). p.310-319- Abstract
- Intranasal administration of peptide Acl-9[4Y], based on the N-terminal epitope of myelin basic protein, can induce CD4(+) T cell tolerance, and suppress experimental autoimmune encephalomyelitis induction. The peptide-induced regulatory T (PI-T-Reg) cells failed to produce IL-2, but expressed IL-10 in response to Ag and could suppress naive T cell responses in vitro. Analysis of Jak-STAT signaling pathways revealed that the activation of Jak1, STAT3, and STAT5 were induced in tolerant T cells after Ag stimulation in vivo. In addition, the expression of suppressor of cytokine signaling 3 was induced in tolerant T cells, suggesting that cytokines regulate the tolerant state of the PI-T-Reg cells. Stimulation of PI-T-Reg cells in vitro with... (More)
- Intranasal administration of peptide Acl-9[4Y], based on the N-terminal epitope of myelin basic protein, can induce CD4(+) T cell tolerance, and suppress experimental autoimmune encephalomyelitis induction. The peptide-induced regulatory T (PI-T-Reg) cells failed to produce IL-2, but expressed IL-10 in response to Ag and could suppress naive T cell responses in vitro. Analysis of Jak-STAT signaling pathways revealed that the activation of Jak1, STAT3, and STAT5 were induced in tolerant T cells after Ag stimulation in vivo. In addition, the expression of suppressor of cytokine signaling 3 was induced in tolerant T cells, suggesting that cytokines regulate the tolerant state of the PI-T-Reg cells. Stimulation of PI-T-Reg cells in vitro with IL-10 induced Jak1 and STAT3 activation, but not STAT5, suggesting that IL-10 is important, but not the only cytokine involved in the development of T cell tolerance. Although IL-2 expression was deficient, stimulation with IL-2 in vitro induced Jak1 and STAT5 activation in PI-T-Reg cells, restored their proliferative response to antigenic stimulation, and abrogated PI-T-Reg-mediated suppression in vitro. However, the addition of IL-2 could not suppress IL-10 expression, and the IL-2 gene remained inactive. After withdrawal of IL-2, the PI-T-Reg cells regained their nonproliferative state and suppressive ability. These results underline the ability of the immune system to maintain tolerance to autoantigens, but at the same time having the ability to overcome the suppressive phenotype of tolerant T cells by cytokines, such as IL-2, during the protective immune response to infection. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/258392
- author
- organization
- publishing date
- 2005
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Immunology
- volume
- 174
- issue
- 1
- pages
- 310 - 319
- publisher
- American Association of Immunologists
- external identifiers
-
- wos:000225852900036
- pmid:15611254
- ISSN
- 1550-6606
- language
- English
- LU publication?
- yes
- id
- 47c60f12-cff1-4ed9-9026-124810143574 (old id 258392)
- alternative location
- http://www.jimmunol.org/cgi/content/abstract/174/1/310
- date added to LUP
- 2016-04-01 15:36:09
- date last changed
- 2018-11-21 20:35:19
@article{47c60f12-cff1-4ed9-9026-124810143574,
abstract = {{Intranasal administration of peptide Acl-9[4Y], based on the N-terminal epitope of myelin basic protein, can induce CD4(+) T cell tolerance, and suppress experimental autoimmune encephalomyelitis induction. The peptide-induced regulatory T (PI-T-Reg) cells failed to produce IL-2, but expressed IL-10 in response to Ag and could suppress naive T cell responses in vitro. Analysis of Jak-STAT signaling pathways revealed that the activation of Jak1, STAT3, and STAT5 were induced in tolerant T cells after Ag stimulation in vivo. In addition, the expression of suppressor of cytokine signaling 3 was induced in tolerant T cells, suggesting that cytokines regulate the tolerant state of the PI-T-Reg cells. Stimulation of PI-T-Reg cells in vitro with IL-10 induced Jak1 and STAT3 activation, but not STAT5, suggesting that IL-10 is important, but not the only cytokine involved in the development of T cell tolerance. Although IL-2 expression was deficient, stimulation with IL-2 in vitro induced Jak1 and STAT5 activation in PI-T-Reg cells, restored their proliferative response to antigenic stimulation, and abrogated PI-T-Reg-mediated suppression in vitro. However, the addition of IL-2 could not suppress IL-10 expression, and the IL-2 gene remained inactive. After withdrawal of IL-2, the PI-T-Reg cells regained their nonproliferative state and suppressive ability. These results underline the ability of the immune system to maintain tolerance to autoantigens, but at the same time having the ability to overcome the suppressive phenotype of tolerant T cells by cytokines, such as IL-2, during the protective immune response to infection.}},
author = {{Anderson, Per and Sundstedt, A and Yazici, Z and Minaee, S and Woolf, R and Nicolson, K and Whitley, N and Li, Li and Li, Su-Ling and Wraith, DC and Wang, Ping}},
issn = {{1550-6606}},
language = {{eng}},
number = {{1}},
pages = {{310--319}},
publisher = {{American Association of Immunologists}},
series = {{Journal of Immunology}},
title = {{IL-2 overcomes the unresponsiveness but fails to reverse the regulatory function of antigen-induced T regulatory cells}},
url = {{http://www.jimmunol.org/cgi/content/abstract/174/1/310}},
volume = {{174}},
year = {{2005}},
}