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 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.
Kecha
O
O
Institute of Pathology CHU-B23, University of Liège, Belgium.
Brilot
F
F
Martens
H
H
Franchimont
N
N
Renard
C
C
Greimers
R
R
Defresne
M P
MP
Winkler
R
R
Geenen
V
V
D000818:Animals; D015139:Blotting, Southern; D002454:Cell Differentiation / Q000502:physiology; D005260:Female; D005434:Flow Cytometry; D017403:In Situ Hybridization; D007335:Insulin-Like Growth Factor II / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D009924:Organ Culture Techniques; D011247:Pregnancy; D012333:RNA, Messenger / Q000096:biosynthesis; D017451:Receptors, Somatomedin / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology; D013002:Somatomedins / Q000502:physiology*; D013601:T-Lymphocytes / Q000502:physiology; D013950:Thymus Gland / Q000166:cytology* / Q000196:embryology*
D012333:RNA, Messenger; D017451:Receptors, Somatomedin; D013002:Somatomedins; D007335:Insulin-Like Growth Factor II