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 journalArticlepeer-review

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

ASJC Scopus subject areas

  • Immunology

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