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Involvement of Insulin-Like Growth Factors in Early T Cell Development: A Study Using Fetal Thymic Organ Cultures¹

Institute of Pathology CHU-B23 (O.K., F.B., H.M., N.F., C.R., V.G.), Laboratory of Radio-Immunology & Neuroendocrine-Immunology, Cell Pathology (R.G.), Histology and Cytology (M.-P.D.), Molecular Oncology (R.W.), University of Liège, B-4000 Liège 1-Sart Tilman, Belgium

Address all correspondence and requests for reprints to: Vincent Geenen, M.D., Ph.D., Institute of Pathology CHU-B23, University of Liège, B-4000 Liège 1-Sart Tilman, Belgium. E-mail: vgeenen{at}ulg.ac.be

The expression of insulin-like growth factor (IGF) and IGF receptor genes was investigated by RT-PCR during ontogeny of the murine thymus. IGF-1, IGF-1R, M6P/IGF-2R genes are expressed in the thymus both in fetal and postnatal life, whereas IGF-2 messenger RNAs (mRNAs) decline after birth but are still detectable on the seventh week. By in situ hybridization, IGF-2 transcripts were located in the outer cortex and medulla of the postnatal thymus, and on the whole surface of the epithelial-like network in the fetal thymus. The effects of anti-IGFs and IGF-receptors neutralizing Abs on the generation of pre-T cell subpopulations were then investigated using fetal thymic organ cultures (FTOC). FTOC treatment with an anti-IGF-2 mAb, an anti-IGF-1R mAb, or an anti-M6P/IGF-2R polyclonal Ab induced a blockade of T cell differentiation at the CD4^-CD8^- stage, as shown by a significant increase in the percentage of CD4^-CD8^- cells and a decrease in the percentage of CD4⁺CD8⁺ cells. Moreover, anti-IGF-2 Ab treatment induced an increase in CD8⁺ cells suggesting that thymic IGF-2 might have a role in determining differentiation into the CD4 or CD8 lineage. Anti-IGF-1 Ab treatment decreased the proportion in CD4^-CD8^- cells and increased the frequency in CD4⁺CD8⁺. FTOC treatment with anti-(pro)insulin did not exert any significant effect on T cell development. These data indicate that the intrathymic IGF-mediated signaling plays an active role in the early steps of T cell differentiation during fetal development.

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