| Autor: |
Laura Strauss, Malgorzata Czystowska, Marta Szajnik, Magis Mandapathil, Theresa L Whiteside |
| Jazyk: |
angličtina |
| Rok vydání: |
2009 |
| Předmět: |
|
| Zdroj: |
PLoS ONE, Vol 4, Iss 6, p e5994 (2009) |
| Druh dokumentu: |
article |
| ISSN: |
1932-6203 |
| DOI: |
10.1371/journal.pone.0005994 |
| Popis: |
The immunosuppressive drug rapamycin (RAPA) promotes the expansion of CD4(+) CD25(high)Foxp3(+) regulatory T cells via mechanisms that remain unknown. Here, we studied expansion, IL-2R-gamma chain signaling, survival pathways and resistance to apoptosis in human Treg responding to RAPA.CD4(+)CD25(+) and CD4(+)CD25(neg) T cells were isolated from PBMC of normal controls (n = 21) using AutoMACS. These T cell subsets were cultured in the presence of anti-CD3/CD28 antibodies and 1000 IU/mL IL-2 for 3 to 6 weeks. RAPA (1-100 nM) was added to half of the cultures. After harvest, the cell phenotype, signaling via the PI3K/mTOR and STAT pathways, expression of survival proteins and Annexin V binding were determined and compared to values obtained with freshly-separated CD4(+)CD25(high) and CD4(+)CD25(neg) T cells. Suppressor function was tested in co-cultures with autologous CFSE-labeled CD4(+)CD25(neg) or CD8(+)CD25(neg) T-cell responders. The frequency and suppressor activity of Treg were increased after culture of CD4(+)CD25(+) T cells in the presence of 1-100 nM RAPA (p |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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