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*
DNAX Research Institute, Palo Alto, CA 94304; and
Institut National de la Santé et de la Recherche Médicale Unit 343 Hôpital de l’Archet, Nice, France
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-
T
cells as the absolute number of thymic dendritic, TCR-
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.
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