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首页> 外文期刊>Clinical and Experimental Immunology: An Official Journal of the British Society for Immunology >Exploring the feasibility of selective depletion of T lymphocyte subsets by whole blood immunoadsorption cytapheresis.
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Exploring the feasibility of selective depletion of T lymphocyte subsets by whole blood immunoadsorption cytapheresis.

机译：探索通过全血免疫吸附细胞分选术选择性清除T淋巴细胞亚群的可行性。

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Normal turnover of T lymphocytes is slow relative to other blood cells. Consequently, the physical removal of circulating leucocytes by thoracic duct drainage, repeated leukapheresis or blood filtration results in T cell depletion and immunosuppression. However, clinical use of such procedures is impractical compared with immunosuppressive drugs or radiation. None the less, immunosuppression by physical depletion of T cells, avoiding the systemic toxicities of drugs and radiation, might have clinical advantages if immunophenotypically distinct T cell subsets could be depleted selectively. Recent advances in targeted plasma protein apheresis using adsorbent macrobead columns prompted us to determine whether analogous techniques might permit CD4+ T lymphocytes to be removed selectively from whole blood. To explore this possibility, we linked murine anti-human-CD4 and isotype-identical control monoclonal antibodies (mAbs) to agarose, polyacrylamide and polystyrene macrobeads (150-350 microm) and then evaluated the selectivity, specificity and efficiency of macrobead columns to remove CD4+ T cells from anti-coagulated whole blood at varying mAb densities and flow rates. We also examined saturation kinetics and Fc-oriention versus random coupling of mAbs to macrobeads. Sepharose 6MB macrobead (250-350 microm) columns proved to be most effective, selectively removing up to 98% of CD4+ T cells from whole blood. Moreover, depletion efficiency and selectivity were retained when these columns were reused after elution of adherent CD4+ cells. These studies indicate that selective depletion of T lymphocyte subsets by whole blood immunoadsorption apheresis using mAb-linked macrobead columns may be feasible on a clinical scale. It is possible that such apheresis techniques could achieve targeted forms of immunosuppression not possible with drugs or radiation.
机译：相对于其他血细胞，T淋巴细胞的正常周转速度较慢。因此，通过胸导管引流，反复的白细胞去除术或血液过滤来物理去除循环中的白细胞会导致T细胞耗竭和免疫抑制。然而，与免疫抑制药物或放射线相比，此类手术的临床使用是不切实际的。尽管如此，如果可以选择性地消除免疫表型不同的T细胞亚群，通过物理消耗T细胞进行免疫抑制，避免药物和放射线的全身毒性可能具有临床优势。使用吸附性大珠色谱柱进行靶向血浆蛋白单采的最新进展促使我们确定类似技术是否可能允许从全血中选择性去除CD4 + T淋巴细胞。为了探索这种可能性，我们将鼠抗人CD4和同种型相同的对照单克隆抗体（mAb）与琼脂糖，聚丙烯酰胺和聚苯乙烯大珠（150-350微米）相连，然后评估了去除大珠柱的选择性，特异性和效率来自抗凝全血的CD4 + T细胞，具有不同的mAb密度和流速。我们还检查了饱和动力学和Fc取向与mAb与大珠的随机偶联的关系。 Sepharose 6MB macrobead（250-350 microm）色谱柱被证明是最有效的，可从全血中选择性去除高达98％的CD4 + T细胞。此外，洗脱贴壁的CD4 +细胞后重新使用这些色谱柱时，保留了耗尽效率和选择性。这些研究表明，使用mAb连接的大珠子色谱柱通过全血免疫吸附血液分离术选择性清除T淋巴细胞亚群在临床规模上是可行的。这种单采血液分离术技术有可能实现药物或放射治疗无法实现的靶向免疫抑制形式。

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