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Reconstitution of FOXP 3 regulatory T cells ( Tregs ) after CD 25-depleted allotransplantion in elderly patients and association with acute graft-versus-host disease
| Content Provider | Semantic Scholar |
|---|---|
| Author | Mielke, Stephan Rezvani, K. Savani, Bipin N. Nunes, Raquel Coronato Yong, Agnes S. M. Schindler, John Kurlander, Roger Ghetie, Victor F. Read, Elizabeth J. Solomon, Scott R. Vitetta, Ellen S. Barrett, Austin John |
| Copyright Year | 2007 |
| Abstract | Selective depletion (SD) of host-reactive donor T cells from allogeneic stem-cell transplants (SCTs) using an anti-CD25 immunotoxin (IT) is a strategy to prevent acute graft-versus-host disease (aGvHD). There is concern that concurrent removal of regulatory T cells (Tregs) with incomplete removal of alloactivated CD25 T cells could increase the risk of aGvHD. We therefore measured Tregs in the blood of 16 patients receiving a T-cell–depleted allograft together with anti–CD25-IT– treated SD lymphocytes, in 13 of their HLA-identical donors, and in 10 SD products. Tregs were characterized by intracellular staining for forkhead box protein 3 (FOXP3) and by quantitative reversetranscription–polymerase chain reaction (qRT-PCR) for FOXP3 gene in CD4 cells. Patients received a median of 1.0 108/ kg SD T cells and a stem cell product containing a median of 0.25 104/kg residual T cells. Tregs reconstituted promptly after SCT and underwent further expansion. Of the CD4 T cells in SD products, 1.5% to 4.8% were CD25 Tregs. Acute GvHD (> grade II) was restricted to 5 patients whose donors had significantly (P .019) fewer Tregs compared with those without clinically significant aGvHD. These results suggest that rapid Treg reconstitution can occur following SD allografts, either from CD25 Tregs escaping depletion, or from residual CD25 and CD25 Tregs contained in the stem-cell product that expand after transplantation and may confer additional protection against GvHD. (Blood. 2007;110:1689-1697) |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://www.bloodjournal.org/content/bloodjournal/110/5/1689.full.pdf?sso-checked=true |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |