Teschner, D. and Distler, E. and Wehler, D. and Frey, M. and Marandiuc, D. and Langeveld, K. and Theobald, M. and Thomas, S. and Herr, W. (2014) Depletion of naive T cells using clinical grade magnetic CD45RA beads: a new approach for GVHD prophylaxis. BONE MARROW TRANSPLANTATION, 49 (1). pp. 138-144. ISSN 0268-3369, 1476-5365
Full text not available from this repository. (Request a copy)Abstract
Depletion of naive T cells from donor leukapheresis products (LPs) aims at the reduction of alloreactivity, while preserving memory T-cell reactivity (for example, to pathogens). This study established the immunomagnetic depletion procedure under clean room conditions using CD45RA beads and analyzed LPs of six donors for cell composition and functional immune responses. CD45RA depletion resulted in 3.4-4.7 log (median 4.4) reduction of CD45RA(+) T cells, thereby eliminating naive and late effector T cells. B cells were also completely removed, whereas significant proportions of NK cells, monocytes and granulocytes persisted. CD45RA-depleted LPs contained effector and central memory CD4(+) and CD8(+) T cells that showed sustained IFN-gamma secretion to CMV, EBV, Aspergillus and Candida Ags. Alloreactivity was measured in MLRs between donors with complete HLA-mismatch. Alloreactive CD8(+) T cells were strongly reduced (median 41-log) upon CD45RA depletion, whereas alloreactive CD4(+) T cells persisted in significant numbers. In conclusion, clinical grade depletion of CD45RA(+) naive T cells from donor LPs is feasible and highly efficient. The depleted products show sustained CD4(+) and CD8(+) T-cell reactivity to pathogens and effectively reduced CD8-mediated alloreactivity. Prophylactic and preemptive infusions after allogeneic SCT may improve T-cell reconstitution and pathogen-specific immunosurveillance, along with lower risk of inducing GVHD.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ALLOGENEIC TRANSPLANTATION; SELECTIVE DEPLETION; MEMORY; LYMPHOCYTES; IMMUNOTHERAPY; STIMULATION; CD4(+); CTL; CD45RA; naive; memory; T cells; alloreactivity; GVHD |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 29 Nov 2019 13:29 |
| Last Modified: | 29 Nov 2019 13:29 |
| URI: | https://pred.uni-regensburg.de/id/eprint/11089 |
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