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.
Lesourne
Renaud
R
Laboratory of Mammalian Genes and Development, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland, USA.
Uehara
Shoji
S
Lee
Jan
J
Song
Ki-Duk
KD
Li
LiQi
L
Pinkhasov
Julia
J
Zhang
Yongqing
Y
Weng
Nan-Ping
NP
Wildt
Kathryn F
KF
Wang
Lie
L
Bosselut
Remy
R
Love
Paul E
PE
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation; D019070:Cell Lineage / Q000502:physiology*; D002470:Cell Survival; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D011506:Proteins / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D015398:Signal Transduction
D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins; D011948:Receptors, Antigen, T-Cell; C544192:themis protein, mouse