Abstract
CD27 and CD28 have emerged as indicators demarcating the transition of thymocytes through β-selection. We found that CD28 exhibits a greater dynamic range of expression during this phase, thus it was employed to further parse the DN/CD44-compartment in order to assess IL-7 signaling during the β-selection process. Plotting CD28 versus CD25 expression revealed six DN/CD44-populations. OP9-DL1 stromal cell co-culture was used to demonstrate a developmental linkage from DN3a (CD25+CD28-/lo) to DN3b (CD25+CD28+) to DN3c (CD25-CD28+) to DN4a (CD25-CD28+) to double positive (DP) and showed the DN4b (CD25-CD28hi) and DN4c (CD25-CD28-/lo) populations to be inefficient in producing DP cells. Using CD69 as an additional marker to further parse the DN4a population, we found the pre-DP cells to be the CD44-CD25-CD28intCD69-CD4-/loCD8-/lo subset. Using this refined developmental scheme, IL-7Rα expression was found to be transiently upregulated post-β-selection in the DN3b and DN3c subsets; however, this increase did not confer enhanced responsiveness over that observed in the DN3a population. CD28 messenger RNA expression was up-regulated in post-β-selected cells, whereas transcripts for CD27, IL-7Rα and Bcl-2 were lower than that observed in the DN3a population. This study refines the current thymocyte differentiation scheme to allow for more detailed evaluation of events controlling early T-cell development, specifically surrounding the β-selection checkpoint.
Original language | English (US) |
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Pages (from-to) | 387-397 |
Number of pages | 11 |
Journal | International immunology |
Volume | 22 |
Issue number | 5 |
DOIs | |
State | Published - Mar 4 2010 |
Externally published | Yes |
Keywords
- IL-7
- IL-7Rα
- β-selection
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology