Involvement of insulin-like growth factors in early T cell development: A study using fetal thymic organ cultures

The expression of insulin-like growth factor (IGF) and IGF receptor genes w as investigated by RT-PCR during ontogeny of the murine thymus. IGF-1, IGF- 1R, M6P/ICF-2R genes are expressed in the thymus both in fetal and postnata l life, whereas IGF-S messenger RNAs (mRNAs) decline after birth but are st ill detectable on the seventh week. By in situ hybridization, IGF-2 transcr ipts 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 genera tion of pre-T cell subpopulations were then investigated using fetal thymic organ cultures (FTOC). FTOC treatment with an anti-IGF-3 mAb, an anti-IGF- 1R mAb, or an anti-M6P/IGF-2R polyclonal Ab induced a blockade of T cell di fferentiation at the CD4(-)CD8(-) stage, as shown by a significant increase in the percentage of CD4(-)CD8(-) cells and a decrease in the percentage o f CD4(+) CD8(+) cells. Moreover, anti-IGF-a Ab treatment induced an increas e in CD8(+) cells suggesting that thymic IGF-S might have a role in determi ning differentiation into the CD4 or CD8 lineage. Anti-IGF-l Ab treatment d ecreased the proportion in CD4(-)CD8(-) cells and increased the frequency i n CD4(+) CD8(+). FTOC treatment with anti-(pro)insulin did not exert any si gnificant effect on T cell development. These data indicate that the intrat hymic IGF-mediated signaling plays an active role in the early steps of T c ell differentiation during fetal development.