Development of immature thymocytes: initiation of CD3, CD4, and CD8 acquisition parallels down-regulation of the interleukin 2 receptor alpha chain.
We have previously identified a developmental sequence among immature thymocytes, prior to their expression of the lineage markers CD3, CD4, and CD8. This sequence is marked by transient expression of the interleukin 2 receptor alpha chain (IL 2R alpha). The most mature cells in this sequence (surface phenotype heat-stable antigen (HSA)++ Pgp-1- IL 2R alpha-) are the immediate precursors to CD4+CD8+ small cortical thymocytes, and have by definition been considered to be CD4-CD8-. We now show that these cells display low levels of surface CD4 and CD8, but not CD3. This low-level expression begins to appear immediately after the loss of IL 2R alpha expression. Northern blot analysis for mRNA expression confirms that these IL 2R alpha- cells are transcribing CD4 and CD8 mRNA, in contrast to their immediate (IL 2R alpha+) precursor. Upon unstimulated culture, these IL 2R alpha- cells gradually acquire high levels of CD4 and CD8, as well as low levels of CD3, whereas IL 2R alpha+ cells do not. These findings suggest that the IL 2R alpha+ subset is the end of the true CD3-CD4-CD8- phase, and that the intracellular signals for CD3, CD4, and CD8 acquisition occur simultaneously with, or immediately prior to, the signal for down-regulation of IL 2R alpha.
Petrie
H T
HT
Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.
Pearse
M
M
Scollay
R
R
Shortman
K
K
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics / Q000378:metabolism*; D015152:Blotting, Northern; D017252:CD3 Complex; D015704:CD4 Antigens / Q000235:genetics / Q000378:metabolism*; D016827:CD8 Antigens; D002454:Cell Differentiation; D005434:Flow Cytometry; D051379:Mice; D008810:Mice, Inbred C57BL; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D015375:Receptors, Interleukin-2 / Q000235:genetics; D013601:T-Lymphocytes / Q000166:cytology*; D013950:Thymus Gland / Q000166:cytology
D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2