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

• DOI: 10.1210/endo.141.3.7360
• Publication Date: 2014-01-08T16:10:55Z
• Authors: Ouafae Kecha; Fabienne Brilot; Henri Martens; Nathalie Franchimont; Chantal Renard; Roland Greimers; Marie-Paule Defresne; Rosita Winkler; Vincent Geenen
• Keywords: 0301 basic medicine; Mice, Inbred BALB C; Reverse Transcriptase Polymerase Chain Reaction; T-Lymphocytes; Cell Differentiation; Receptors, Somatomedin; Thymus Gland; Flow Cytometry; 3. Good health; Blotting, Southern; Mice; 03 medical and health sciences; Organ Culture Techniques; Insulin-Like Growth Factor II; Pregnancy; Somatomedins; Animals; Female; RNA, Messenger; In Situ Hybridization; Signal Transduction

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 ofthe 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.