The ThPOK transcription factor differentially affects the development and function of self-specific CD8(+) T cells and regulatory CD4(+) T cells.
The zinc finger transcription factor ThPOK plays a crucial role in CD4 T-cell development and CD4/CD8 lineage decision. In ThPOK-deficient mice, developing T cells expressing MHC class II-restricted T-cell receptors are redirected into the CD8 T-cell lineage. In this study, we investigated whether the ThPOK transgene affected the development and function of two additional types of T cells, namely self-specific CD8 T cells and CD4(+) FoxP3(+) T regulatory cells. Self-specific CD8 T cells are characterized by high expression of CD44, CD122, Ly6C, 1B11 and proliferation in response to either IL-2 or IL-15. The ThPOK transgene converted these self-specific CD8 T cells into CD4 T cells. The converted CD4(+) T cells are no longer self-reactive, lose the characteristics of self-specific CD8 T cells, acquire the properties of conventional CD4 T cells and survive poorly in peripheral lymphoid organs. By contrast, the ThPOK transgene promoted the development of CD4(+) FoxP3(+) regulatory T cells resulting in an increased recovery of CD4(+) FoxP3(+) regulatory T cells that expressed higher transforming growth factor-β-dependent suppressor activity. These studies indicate that the ThPOK transcription factor differentially affects the development and function of self-specific CD8 T cells and CD4(+) FoxP3(+) regulatory T cells.
Department of Biotechnology and Laboratory Science in Medicine, National Yang-Ming University, Taipei, Taiwan.
Yuh-Ching
YC
Twu
Hung-Sia
HS
Teh
D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006182:H-Y Antigen / Q000378:metabolism; D018960:Hyaluronan Receptors / Q000378:metabolism; D019409:Interleukin-15 / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D053646:Interleukin-2 Receptor beta Subunit / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D011946:Receptors, Antigen / Q000378:metabolism; D017634:Self Tolerance; D012737:Sex Factors; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism*; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism
D000950:Antigens, Ly; D015415:Biomarkers; C476399:Cd44 protein, mouse; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D006182:H-Y Antigen; C028507:H-Y antigen receptor; D018960:Hyaluronan Receptors; C508022:Il2rb protein, mouse; D019409:Interleukin-15; D007376:Interleukin-2; D053646:Interleukin-2 Receptor beta Subunit; C494192:Ly-6C antigen, mouse; D011946:Receptors, Antigen; D014157:Transcription Factors; D016212:Transforming Growth Factor beta
ThPOK; forkhead box protein 3; regulatory T cells; self-specific CD8 T cells