TCR-gamma genes are rearranged but not transcribed in IL-7R alpha-deficient mice.
IL-7, a cytokine produced by bone marrow and thymic stroma, is a growth factor for B and T lymphocytes very early in their development. The IL-7R is a heterodimer of an alpha-chain that specifically binds IL-7 and the common gamma-chain, gamma(c), which is also a component of the receptors for IL-2, IL-4, IL-9, and IL-15. IL-7 has also been hypothesized to play a role in the differentiation of gammadelta T cells, which is supported by the recent findings that mice deficient in the alpha-chain of the IL-7R (IL-7R alpha -/-) or IL-7 (IL-7 -/-) have a complete absence of gammadelta T cells, but not alphabeta T cells. We show in this work that Vgamma4 and Vgamma6 TCR genes are rearranged, and sterile Vgamma4 and Vgamma6 TCR-gamma transcripts are expressed in IL-7R alpha -/- thymocytes, but these TCR-gamma genes, and Vgamma5, are not transcribed in thymocytes from IL-7R alpha -/- mice. RAG-1 and RAG-2 genes are transcriptionally active in fetal and adult IL-7R alpha -/- thymocytes. The IL-7-inducible transcription factor, STAT5, is not active in the fetal thymus of IL-7R alpha -/- compared with IL-7R alpha +/+ mice. These data point to a specific role for IL-7/IL-7R signaling in regulating the transcriptional activity, possibly mediated by STAT5, of the rearranged TCR-gamma complex during development of gammadelta T cells, and point to mechanistic differences in the regulation of rearrangement of Vgamma4 and Vgamma6 genes vs Vgamma5.
Perumal
N B
NB
The University of Pittsburgh Cancer Institute and Department of Pathology, University of Pittsburgh School of Medicine, PA 15213, USA.
Kenniston
T W
TW
Tweardy
D J
DJ
Dyer
K F
KF
Hoffman
R
R
Peschon
J
J
Appasamy
P M
PM
D000818:Animals; D004268:DNA-Binding Proteins / Q000032:analysis; D005260:Female; D015334:Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor / Q000235:genetics*; D015851:Interleukin-7; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008894:Milk Proteins; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis; D018123:Receptors, Interleukin / Q000172:deficiency*; D050799:STAT5 Transcription Factor; D015534:Trans-Activators / Q000032:analysis; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D015851:Interleukin-7; D008894:Milk Proteins; D016692:Receptors, Antigen, T-Cell, gamma-delta; D018123:Receptors, Interleukin; D050799:STAT5 Transcription Factor; C000589613:T-cell receptor Vgamma6, mouse; D015534:Trans-Activators