Positive selection by the pre-TCR yields mature CD8+ T cells.
It has been of much interest whether there is functional redundancy between the constitutively signaling pre-Talpha/TCRbeta (pre-TCR) and ligated TCRalphabeta complexes, which independently operate the two distinct checkpoints during thymocyte development, i.e., the pre-TCR involved in beta-selection at the CD4(-)CD8(-) double-negative stage and the TCRalphabeta being crucial for positive/negative selection at the CD4(+)CD8(+) double-positive stage. We found that the pre-TCR expressed on double-positive cells in TCRalpha-deficient (TCRalpha(-/-)) mice produced a small number of mature CD8(+) T cells. Surprisingly, when pre-Talpha was overexpressed, resulting in augmentation of pre-TCR expression, there was a striking increase of the CD8(+) T cells. In addition, even in the absence of up-regulation of pre-TCR expression, a similar increase of CD8(+) T cells was also observed in TCRalpha(-/-) mice overexpressing Egr-1, which lowers the threshold of signal strength required for positive selection. In sharp contrast, the CD8(+) T cells drastically decreased in the absence of pre-Talpha on a TCRalpha(-/-) background. Thus, the pre-TCR appears to functionally promote positive selection of CD8(+) T cells. The biased production of CD8(+) T cells via the pre-TCR might also support the potential involvement of signal strength in CD4/CD8 lineage commitment.
Ito
Yuriko
Y
Center for Immunology, University of Texas Southwestern Medical Center, Dallas 75390, USA.
Arai
Satoko
S
van Oers
Nicolai S C
NS
Aifantis
Iannis
I
von Boehmer
Harald
H
Miyazaki
Toru
T
D000276:Adjuvants, Immunologic / Q000502:physiology; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D004268:DNA-Binding Proteins / Q000502:physiology; D051766:Early Growth Response Protein 1; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000502:physiology; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000502:physiology; D017874:Immediate-Early Proteins; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000235:genetics; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016693:Receptors, Antigen, T-Cell, alpha-beta; D014157:Transcription Factors / Q000502:physiology
D000276:Adjuvants, Immunologic; D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D017874:Immediate-Early Proteins; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D014157:Transcription Factors; C090377:pre-T cell receptor alpha