IL-10 transgenic mice present a defect in T cell development reminiscent of SCID patients.
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-alpha beta T cells as the absolute number of thymic dendritic, TCR-gamma delta 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.
Rouleau
M
M
DNAX Research Institute, Palo Alto, CA 94304, USA.
Cottrez
F
F
Bigler
M
M
Antonenko
S
S
Carballido
J M
JM
Zlotnik
A
A
Roncarolo
M G
MG
Groux
H
H
D000818:Animals; D000831:Animals, Newborn / Q000235:genetics / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology; D005333:Fetus; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics*; D007694:Killer Cells, Natural / Q000166:cytology / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic / Q000276:immunology*; D009924:Organ Culture Techniques; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics; D016511:Severe Combined Immunodeficiency / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D013234:Stem Cells / Q000276:immunology / Q000473:pathology; D017154:Stromal Cells / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology*; D013950:Thymus Gland / Q000276:immunology / Q000473:pathology
D016692:Receptors, Antigen, T-Cell, gamma-delta; D016753:Interleukin-10