Perturbation of the T Lymphocyte Lineage In Transgenic Mice Expressing a Constitutive Repressor of Nuclear Factor (NF)-κB
Open Access
- 2 June 1997
- journal article
- Published by Rockefeller University Press in The Journal of Experimental Medicine
- Vol. 185 (11) , 1897-1907
- https://doi.org/10.1084/jem.185.11.1897
Abstract
Members of the nuclear factor (NF)-κB/Rel family transcription factors are induced during thymic selection and in mature T lymphocytes after ligation of the T cell antigen receptor (TCR). Despite these findings, disruption of individual NF-κB/Rel genes has revealed no intrinsic defect in the development of mature T cells, perhaps reflecting functional redundancy. To circumvent this possibility, the T cell lineage was targeted to express a trans-dominant form of IκBα that constitutively represses the activity of multiple NF-κB/Rel proteins. Transgenic cells expressing this inhibitor exhibit a significant proliferative defect, which is not reversed by the addition of exogenous interleukin-2. Moreover, mitogenic stimulation of splenocytes leads to increased apoptosis of transgenic T cells as compared with controls. In addition to deregulated T cell growth and survival, transgene expression impairs the development of normal T cell populations as evidenced by diminished numbers of TCRhi CD8 single-positive thymocytes. This defect was significantly amplified in the periphery and was accompanied by a decrease in CD4+ T cells. Taken together, these in vivo findings indicate that the NF-κB/Rel signaling pathway contains compensatory components that are essential for the establishment of normal T cell subsets.Keywords
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