BCL-2 allows effector and memory CD8+ T cells to tolerate higher expression of BIM (104.19)
| Autor: | Sema Kurtulus, Pulak Tripathi, Maria Moreno-Fernandez, Allyson Sholl, Jonathan Katz, Harry Grimes, David Hildeman |
|---|---|
| Rok vydání: | 2011 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 186:104.19-104.19 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | As acute infections resolve, most effector CD8+ T cells die, while some persist and become memory T cells. Recent work showed that subsets of effector CD8+ T cells, identified by reciprocal expression of KLRG1 and CD127, have different lifespans. Similar to previous reports, we found that effector CD8+ T cells reported to have a longer lifespan (i.e. KLRG1lo CD127hi) have increased levels of Bcl-2 compared to their shorter lived KLRG1hi CD127lo counterparts. Surprisingly, we found that these effector KLRG1lo CD127hi CD8+ T cells also had increased levels of Bim compared to KLRG1hi CD127lo cells. Similarly, central memory CD8+ T cells (TCM) expressed higher levels of Bim and Bcl-2 than did effector memory CD8+ T cells (TEM). Using both pharmacologic and genetic approaches, we found that survival of both subsets of effector and memory CD8+ T cells required Bcl-2 to combat the pro-apoptotic activity of Bim. Interestingly, inhibition or absence of Bcl-2 led to significantly decreased expression of Bim in surviving effector and memory T cells. In addition, manipulation of Bcl-2 levels by IL-7 or IL-15 also affected expression of Bim in effector CD8+ T cells. Finally, we found that Bim levels were significantly increased in effector CD8+ T cells lacking Bax and Bak. Together, these data indicate that cells having the highest levels of Bim are selected against during contraction of the response and that Bcl-2 determines the level of Bim that effector and memory T cells can tolerate. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|