| First Author | Van De Wiele CJ | Year | 2004 |
| Journal | J Immunol | Volume | 172 |
| Issue | 7 | Pages | 4235-44 |
| PubMed ID | 15034036 | Mgi Jnum | J:89622 |
| Mgi Id | MGI:3040866 | Doi | 10.4049/jimmunol.172.7.4235 |
| Citation | Van De Wiele CJ, et al. (2004) Thymocytes between the beta-selection and positive selection checkpoints are nonresponsive to IL-7 as assessed by STAT-5 phosphorylation. J Immunol 172(7):4235-44 |
| abstractText | Interleukin-7 is widely accepted as a major homeostatic factor involved in T cell development. To assess the IL-7 responsiveness of thymocytes involved in selection processes, we used a new sensitive flow cytometry-based assay to detect intracellular phosphorylation of STAT-5 induced by IL-7 in defined mouse thymocyte subsets. Using this method, we found the earliest thymocyte subset (CD4(-)CD8(-)CD25(-)CD44(+)) to contain both IL-7-responsive and nonresponsive cells. Transition through the next stages of development (CD4(-)CD8(-)CD25(+)CD44(+ and -)) was associated with responsiveness of all thymocytes within these populations. Passage of thymocytes through beta-selection resulted in a significant reduction in IL-7 sensitivity. In the next phases of development (TCR(-) and TCR(low)CD69(-)), thymocytes were completely insensitive to the effects of IL-7. STAT-5 phosphorylation in response to IL-7 was again observed, however, in thymocytes involved in the positive selection process (TCR(low)CD69(+) and TCR(intermediate)). As expected, CD4 and CD8 single-positive thymocytes were responsive to IL-7. These findings delineate an IL-7-insensitive population between the beta-selection and positive selection checkpoints encompassing thymocytes predicted to die by neglect due to failure of positive selection. This pattern of sensitivity suggests a two-signal mechanism by which survival of thymocytes at these checkpoints is governed. |
