Themis, a T cell–specific protein important for late thymocyte development

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Abstract
The molecular mechanisms that underpin thymocyte selection remain incompletely defined. Groups led by Love, Gascoigne and Schwartz independently identify Themis, a signaling protein essential for the positive selection of thymocytes. 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+CD8int thymocytes as well as CD4+ or CD8+ single-positive thymocytes was lower. Notably, although we detected no overt TCR-proximal signaling deficiencies, Themis−/− CD4+CD8int 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.