TOX is required for development of the CD4 T cell lineage gene program.
The factors that regulate thymic development of the CD4(+) T cell gene program remain poorly defined. The transcriptional regulator ThPOK is a dominant factor in CD4(+) T cell development, which functions primarily to repress the CD8 lineage fate. Previously, we showed that nuclear protein TOX is also required for murine CD4(+) T cell development. In this study, we sought to investigate whether the requirement for TOX was solely due to a role in ThPOK induction. In apparent support of this proposition, ThPOK upregulation and CD8 lineage repression were compromised in the absence of TOX, and enforced ThPOK expression could restore some CD4 development. However, these "rescued" CD4 cells were defective in many aspects of the CD4(+) T cell gene program, including expression of Id2, Foxo1, and endogenous Thpok, among others. Thus, TOX is necessary to establish the CD4(+) T cell lineage gene program, independent of its influence on ThPOK expression.
Research Division of Immunology, Department of Biomedical Sciences, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Parinaz
P
Aliahmad
Asha
A
Kadavallore
Brian
B
de la Torre
Dietmar
D
Kappes
Jonathan
J
Kaye
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation / Q000235:genetics* / Q000276:immunology; D019070:Cell Lineage / Q000235:genetics / Q000276:immunology; D002469:Cell Separation; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D015870:Gene Expression / Q000235:genetics / Q000276:immunology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000235:genetics* / Q000276:immunology; D018398:Homeodomain Proteins / Q000235:genetics* / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D060888:Real-Time Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology
D018398:Homeodomain Proteins; D014157:Transcription Factors; C493241:Rhox8 protein, mouse; C497211:Zbtb7b protein, mouse