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© The Rockefeller University Press, 0022-1007/1999/10/973/ $5.00
The Journal of Experimental Medicine, Volume 190, Number 7, October 4, 1999 973-982

Defective Development of {gamma}/{delta} T Cells in Interleukin 7 Receptor–deficient Mice Is Due to Impaired Expression of T Cell Receptor {gamma} Genes

Joonsoo Kanga, Mark Colesa, and David H. Rauleta
a Department of Molecular and Cell Biology and the Cancer Research Laboratory, Division of Immunology, University of California at Berkeley, Berkeley, California 94720

Correspondence to: David H. Raulet, Department of Molecular and Cell Biology, 485 Life Sciences Addition, University of California at Berkeley, Berkeley, CA 94720. Tel:510-642-9521 Fax:510-642-1443 E-mail:raulet{at}uclink4.berkeley.edu.

Mice lacking the interleukin 7 receptor (IL-7R) generate {alpha} 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-7R{alpha}-/- 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-7R{alpha}-/- mice, as well as the effects of IL-7 on transcription of endogenous, rearranged TCR-{gamma} genes in {alpha}/ß 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-7R{alpha}-/- 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-7R{alpha}-/- mice to drive {gamma}/{delta} cell development. The results indicate that the absence of {gamma}/{delta} T cells in IL-7R{alpha}-/- mice is due to insufficient TCR-{gamma} gene expression.

Key Words: T cell development, interleukin 7, lineage commitment, T cell receptor gene rearrangement, transcription


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