Teschner D, Distler E, Wehler D, Frey M, Marandiuc D, Langeveld K, Theobald M, Thomas S, Herr W
Third Department of Medicine-Hematology, Oncology, Pneumology, University Medical Center of Johannes Gutenberg-University, Mainz, Germany.
Transfusion Center, University Medical Center of Johannes Gutenberg-University, Mainz, Germany.
Bone Marrow Transplant. 2014 Jan;49(1):138-44. doi: 10.1038/bmt.2013.114. Epub 2013 Aug 12.
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.
从供体白细胞单采产物（LP）中去除初始T细胞旨在降低同种异体反应性，同时保留记忆T细胞反应性（例如对病原体的反应性）。本研究在洁净室条件下使用CD45RA磁珠建立了免疫磁珠去除程序，并分析了6名供体的LP的细胞组成和功能性免疫反应。CD45RA去除导致CD45RA(+) T细胞减少3.4 - 4.7对数（中位数4.4），从而消除了初始T细胞和晚期效应T细胞。B细胞也被完全去除，而相当比例的NK细胞、单核细胞和粒细胞得以保留。去除CD45RA的LP含有效应性和中枢记忆性CD4(+)和CD8(+) T细胞，这些细胞对巨细胞病毒、EB病毒、曲霉菌和念珠菌抗原持续分泌干扰素-γ。在完全HLA不匹配的供体之间的混合淋巴细胞反应（MLR）中测量同种异体反应性。去除CD45RA后，同种反应性CD8(+) T细胞大幅减少（中位数>1对数），而同种反应性CD4(+) T细胞仍大量存在。总之，从供体LP中临床级去除CD45RA(+)初始T细胞是可行且高效的。去除后的产物对病原体显示出持续的CD4(+)和CD8(+) T细胞反应性，并有效降低了CD8介导的同种异体反应性。异基因造血干细胞移植后的预防性和抢先性输注可能改善T细胞重建和病原体特异性免疫监测，同时降低诱发移植物抗宿主病（GVHD）的风险。
