Ikaros, Helios, and Aiolos protein levels increase in human thymocytes after β selection

JL Mitchell, A Seng, TM Yankee - Immunologic research, 2016 - Springer
JL Mitchell, A Seng, TM Yankee
Immunologic research, 2016Springer
In human T cell development, the mechanisms that regulate cell fate decisions after TCRβ
expression remain unclear. We defined the stages of T cell development that flank TCRβ
expression and found distinct patterns of human T cell development. In half the subjects, T
cell development progressed from the CD4–CD8–double-negative stage to the CD4+ CD8+
double-positive (DP) stage through an immature single-positive (ISP) CD4+ intermediate.
However, in some patients, CD4 and CD8 were expressed simultaneously and the ISP …
Abstract
In human T cell development, the mechanisms that regulate cell fate decisions after TCRβ expression remain unclear. We defined the stages of T cell development that flank TCRβ expression and found distinct patterns of human T cell development. In half the subjects, T cell development progressed from the CD4CD8 double-negative stage to the CD4+CD8+ double-positive (DP) stage through an immature single-positive (ISP) CD4+ intermediate. However, in some patients, CD4 and CD8 were expressed simultaneously and the ISP population was small. In each group of patients, CD3 ISP and DP thymocytes were subdivided into ISP1, ISP2, DP1, DP2, DP3, DP4, and DP5 developmental stages according to their expression of CD28, CD44, CD1a, CD7, CD45RO, and CD38. The ISP2, DP2, and DP3 thymocyte populations proliferated more robustly than ISP1 and DP1 and expressed markers consistent with TCRβ expression. After the DP3 stage, proliferation returned to baseline levels. We then analyzed protein levels of Ikaros, Helios, and Aiolos, the three Ikaros family members most abundantly expressed in human thymocytes. Ikaros and Helios expression increased transiently at the ISP2, DP2, and DP3 populations. Aiolos expression also increased at the ISP2, DP2, and DP3 stages, but its expression remained elevated throughout the DP4 and DP5 stages. In summary, we propose a model of human T cell development that reflects the asynchronous nature of TCRβ expression and we define the subpopulations of thymocytes that are highly proliferative and express Ikaros family members.
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