IL-10 transgenic mice present a defect in T cell development reminiscent to SCID patients

Matthieu Rouleau, Françoise Cottrez, Mike Bigler, Sevtlana Antonenko, José M. Carballido, Albert Zlotnik, Maria Grazia Roncarolo, Hervé Groux

Research output: Contribution to journalArticle

Abstract

To analyze the effect of IL-10 overexpressed by APCs as observed in some SCID patients, we have expressed the human IL-10 cDNA under the control of the murine MHC class II promoter in transgenic mice. Similar to SCID patients, these mice presented a defect in T cell maturation characterized by a rapid thymic aplasia that started after birth. The blockage in T cell maturation was strictly restricted to TCR-αβ T cells as the absolute number of thymic dendritic, TCR-γδ and NK1.1 T cells were equivalent to control littermates. Crossing IL-10 transgenic mice with TCR transgenic mice or treatment with staphylococcal enterotoxin B showed that the defect was not related to the impairment of positive or negative selection. However, repopulating of IL-10 transgenic mouse-fetal thymic organ culture with different stages of triple negative T cells isolated from control mice showed that the blockage occurred specifically at the pre-T cell stage and was reverted by treatment with blocking anti-IL-10 mAbs. These results demonstrate that IL-10 regulates T cell maturation and that dysregulation of IL-10 expression can lead to severe T cell immunodeficiency.

Original languageEnglish
Pages (from-to)1420-1427
Number of pages8
JournalJournal of Immunology
Volume163
Issue number3
Publication statusPublished - Aug 1 1999

Fingerprint

Interleukin-10
Transgenic Mice
T-Lymphocytes
SCID Mice
Organ Culture Techniques
Complementary DNA
Parturition
Therapeutics

ASJC Scopus subject areas

  • Immunology

Cite this

Rouleau, M., Cottrez, F., Bigler, M., Antonenko, S., Carballido, J. M., Zlotnik, A., ... Groux, H. (1999). IL-10 transgenic mice present a defect in T cell development reminiscent to SCID patients. Journal of Immunology, 163(3), 1420-1427.

IL-10 transgenic mice present a defect in T cell development reminiscent to SCID patients. / Rouleau, Matthieu; Cottrez, Françoise; Bigler, Mike; Antonenko, Sevtlana; Carballido, José M.; Zlotnik, Albert; Roncarolo, Maria Grazia; Groux, Hervé.

In: Journal of Immunology, Vol. 163, No. 3, 01.08.1999, p. 1420-1427.

Research output: Contribution to journalArticle

Rouleau, M, Cottrez, F, Bigler, M, Antonenko, S, Carballido, JM, Zlotnik, A, Roncarolo, MG & Groux, H 1999, 'IL-10 transgenic mice present a defect in T cell development reminiscent to SCID patients', Journal of Immunology, vol. 163, no. 3, pp. 1420-1427.
Rouleau M, Cottrez F, Bigler M, Antonenko S, Carballido JM, Zlotnik A et al. IL-10 transgenic mice present a defect in T cell development reminiscent to SCID patients. Journal of Immunology. 1999 Aug 1;163(3):1420-1427.
Rouleau, Matthieu ; Cottrez, Françoise ; Bigler, Mike ; Antonenko, Sevtlana ; Carballido, José M. ; Zlotnik, Albert ; Roncarolo, Maria Grazia ; Groux, Hervé. / IL-10 transgenic mice present a defect in T cell development reminiscent to SCID patients. In: Journal of Immunology. 1999 ; Vol. 163, No. 3. pp. 1420-1427.
@article{a8001b915f21459cb84279f2303cc434,
title = "IL-10 transgenic mice present a defect in T cell development reminiscent to SCID patients",
abstract = "To analyze the effect of IL-10 overexpressed by APCs as observed in some SCID patients, we have expressed the human IL-10 cDNA under the control of the murine MHC class II promoter in transgenic mice. Similar to SCID patients, these mice presented a defect in T cell maturation characterized by a rapid thymic aplasia that started after birth. The blockage in T cell maturation was strictly restricted to TCR-αβ T cells as the absolute number of thymic dendritic, TCR-γδ and NK1.1 T cells were equivalent to control littermates. Crossing IL-10 transgenic mice with TCR transgenic mice or treatment with staphylococcal enterotoxin B showed that the defect was not related to the impairment of positive or negative selection. However, repopulating of IL-10 transgenic mouse-fetal thymic organ culture with different stages of triple negative T cells isolated from control mice showed that the blockage occurred specifically at the pre-T cell stage and was reverted by treatment with blocking anti-IL-10 mAbs. These results demonstrate that IL-10 regulates T cell maturation and that dysregulation of IL-10 expression can lead to severe T cell immunodeficiency.",
author = "Matthieu Rouleau and Fran{\cc}oise Cottrez and Mike Bigler and Sevtlana Antonenko and Carballido, {Jos{\'e} M.} and Albert Zlotnik and Roncarolo, {Maria Grazia} and Herv{\'e} Groux",
year = "1999",
month = "8",
day = "1",
language = "English",
volume = "163",
pages = "1420--1427",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "3",

}

TY - JOUR

T1 - IL-10 transgenic mice present a defect in T cell development reminiscent to SCID patients

AU - Rouleau, Matthieu

AU - Cottrez, Françoise

AU - Bigler, Mike

AU - Antonenko, Sevtlana

AU - Carballido, José M.

AU - Zlotnik, Albert

AU - Roncarolo, Maria Grazia

AU - Groux, Hervé

PY - 1999/8/1

Y1 - 1999/8/1

N2 - To analyze the effect of IL-10 overexpressed by APCs as observed in some SCID patients, we have expressed the human IL-10 cDNA under the control of the murine MHC class II promoter in transgenic mice. Similar to SCID patients, these mice presented a defect in T cell maturation characterized by a rapid thymic aplasia that started after birth. The blockage in T cell maturation was strictly restricted to TCR-αβ T cells as the absolute number of thymic dendritic, TCR-γδ and NK1.1 T cells were equivalent to control littermates. Crossing IL-10 transgenic mice with TCR transgenic mice or treatment with staphylococcal enterotoxin B showed that the defect was not related to the impairment of positive or negative selection. However, repopulating of IL-10 transgenic mouse-fetal thymic organ culture with different stages of triple negative T cells isolated from control mice showed that the blockage occurred specifically at the pre-T cell stage and was reverted by treatment with blocking anti-IL-10 mAbs. These results demonstrate that IL-10 regulates T cell maturation and that dysregulation of IL-10 expression can lead to severe T cell immunodeficiency.

AB - To analyze the effect of IL-10 overexpressed by APCs as observed in some SCID patients, we have expressed the human IL-10 cDNA under the control of the murine MHC class II promoter in transgenic mice. Similar to SCID patients, these mice presented a defect in T cell maturation characterized by a rapid thymic aplasia that started after birth. The blockage in T cell maturation was strictly restricted to TCR-αβ T cells as the absolute number of thymic dendritic, TCR-γδ and NK1.1 T cells were equivalent to control littermates. Crossing IL-10 transgenic mice with TCR transgenic mice or treatment with staphylococcal enterotoxin B showed that the defect was not related to the impairment of positive or negative selection. However, repopulating of IL-10 transgenic mouse-fetal thymic organ culture with different stages of triple negative T cells isolated from control mice showed that the blockage occurred specifically at the pre-T cell stage and was reverted by treatment with blocking anti-IL-10 mAbs. These results demonstrate that IL-10 regulates T cell maturation and that dysregulation of IL-10 expression can lead to severe T cell immunodeficiency.

UR - http://www.scopus.com/inward/record.url?scp=0033179404&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033179404&partnerID=8YFLogxK

M3 - Article

C2 - 10415042

AN - SCOPUS:0033179404

VL - 163

SP - 1420

EP - 1427

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 3

ER -