Themis, a T cell-specific protein important for late thymocyte development.
During positive selection, thymocytes transition through a stage during which T cell antigen receptor (TCR) signaling controls CD4-versus-CD8 lineage 'choice' and subsequent maturation. Here we describe a previously unknown T cell-specific protein, Themis, that serves a distinct function during this stage. In Themis(-/-) mice, thymocyte selection was impaired and the number of transitional CD4(+)CD8(int) thymocytes as well as CD4(+) or CD8(+) single-positive thymocytes was lower. Notably, although we detected no overt TCR-proximal signaling deficiencies, Themis(-/-) CD4(+)CD8(int) thymocytes showed developmental defects consistent with attenuated signaling that were reversible by TCR stimulation. Our results identify Themis as a critical component of the T cell developmental program and suggest that Themis functions to sustain and/or integrate signals required for proper lineage commitment and maturation.
Pubmed ID: 19597498 RIS Download
Animals | CD4-Positive T-Lymphocytes | CD8-Positive T-Lymphocytes | Cell Differentiation | Cell Lineage | Cell Survival | Cells, Cultured | Embryonic Stem Cells | Female | Flow Cytometry | Humans | Mice | Mice, Knockout | Oligonucleotide Array Sequence Analysis | Proteins | Receptors, Antigen, T-Cell | Signal Transduction