6533b85cfe1ef96bd12bd647

RESEARCH PRODUCT

Depletion of naive T cells using clinical grade magnetic CD45RA beads: a new approach for GVHD prophylaxis

K LangeveldMatthias TheobaldEva DistlerDaniela WehlerSimone ThomasD MarandiucDaniel TeschnerWolfgang HerrMichaela Frey

subject

AdultCD4-Positive T-LymphocytesMaleHerpesvirus 4 HumanT-LymphocytesCytomegalovirusGraft vs Host DiseaseEnzyme-Linked Immunosorbent AssayCD8-Positive T-LymphocytesLymphocyte DepletionImmunophenotypingInterferon-gammaInterleukin 21ImmunophenotypingImmune systemAntigenAntigens NeoplasmHumansMedicineLeukapheresisCandidaTransplantationImmunomagnetic Separationbusiness.industryHematologyLeukapheresisFlow Cytometrymedicine.diseaseTransplantationAspergillusGraft-versus-host diseaseImmunologyLeukocyte Common AntigensbusinessCD8

description

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-γ 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 >1-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.

https://doi.org/10.1038/bmt.2013.114