Defective development of gamma/delta T cells in interleukin 7 receptor-deficient mice is due to impaired expression of T cell receptor gamma genes.
Mice lacking the interleukin 7 receptor (IL-7R) generate alpha/beta T cells at a detectable but greatly reduced rate, but gamma/delta T cells are completely absent. The special role of IL-7R signaling in gamma/delta T cell development has remained unclear. IL-7Ralpha(-/-) mice exhibit a paucity of gamma gene rearrangements. This striking observation can be explained by a defect in T cell receptor (TCR)-gamma gene rearrangement, a defect in TCR-gamma gene transcription leading to death of gamma/delta lineage cells, and/or a requirement for IL-7R in commitment of cells to the gamma/delta lineage. To determine the role of IL-7R signaling in gamma/delta T cell development, we examined transcription of a prerearranged TCR-gamma transgene in IL-7Ralpha(-/-) mice, as well as the effects of IL-7 on transcription of endogenous, rearranged TCR-gamma genes in alpha/beta lineage cells. The results demonstrate that IL-7R-mediated signals are necessary for the normal expression of rearranged TCR-gamma genes. Equally significant, the results show that the poor expression of TCR-gamma genes in IL-7Ralpha(-/-) mice is responsible for the selective deficit in gamma/delta cells in these mice, since a high copy TCR-gamma transgene exhibited sufficient residual expression in IL-7Ralpha(-/-) mice to drive gamma/delta cell development. The results indicate that the absence of gamma/delta T cells in IL-7Ralpha(-/-) mice is due to insufficient TCR-gamma gene expression.
Kang
J
J
Department of Molecular and Cell Biology and the Cancer Research Laboratory, Division of Immunology, University of California at Berkeley, Berkeley, California 94720, USA.
Coles
M
M
Raulet
D H
DH
D000818:Animals; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000276:immunology; D015334:Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor; D019675:Genes, T-Cell Receptor gamma; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics* / Q000276:immunology* / Q000502:physiology; D020395:Receptors, Interleukin-7 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology; D014158:Transcription, Genetic
D016692:Receptors, Antigen, T-Cell, gamma-delta; D020395:Receptors, Interleukin-7