Depletion of naive T cells using clinical grade magnetic CD45RA beads: a new approach for GVHD prophylaxis.
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.
Third Department of Medicine-Hematology, Oncology, Pneumology, University Medical Center of Johannes Gutenberg-University, Mainz, Germany.
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Teschner
Third Department of Medicine-Hematology, Oncology, Pneumology, University Medical Center of Johannes Gutenberg-University, Mainz, Germany.
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Distler
Third Department of Medicine-Hematology, Oncology, Pneumology, University Medical Center of Johannes Gutenberg-University, Mainz, Germany.
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Wehler
Third Department of Medicine-Hematology, Oncology, Pneumology, University Medical Center of Johannes Gutenberg-University, Mainz, Germany.
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Frey
Transfusion Center, University Medical Center of Johannes Gutenberg-University, Mainz, Germany.
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Marandiuc
Miltenyi Biotec GmbH, Bergisch Gladbach, Germany.
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Langeveld
Third Department of Medicine-Hematology, Oncology, Pneumology, University Medical Center of Johannes Gutenberg-University, Mainz, Germany.
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Theobald
Third Department of Medicine-Hematology, Oncology, Pneumology, University Medical Center of Johannes Gutenberg-University, Mainz, Germany.
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Thomas
1] Third Department of Medicine-Hematology, Oncology, Pneumology, University Medical Center of Johannes Gutenberg-University, Mainz, Germany [2] Department of Internal Medicine III-Hematology and Oncology, University Medical Center of Regensburg, Regensburg, Germany.
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Herr
D000328:Adult; D000951:Antigens, Neoplasm / Q000378:metabolism; D001230:Aspergillus; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002175:Candida; D003587:Cytomegalovirus; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006086:Graft vs Host Disease / Q000517:prevention & control*; D004854:Herpesvirus 4, Human; D006801:Humans; D018189:Immunomagnetic Separation / Q000379:methods*; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000378:metabolism; D007937:Leukapheresis / Q000379:methods; D017493:Leukocyte Common Antigens / Q000378:metabolism*; D008212:Lymphocyte Depletion / Q000295:instrumentation / Q000379:methods*; D008297:Male; D013601:T-Lymphocytes / Q000276:immunology*
D000951:Antigens, Neoplasm; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens