ATG-Fresenius Inhibits Blood Circulating Cell Proliferation in a Dose-Dependent Manner: An Experimental Study

作者：Werner I; Seitz Merwald I; Kiessling A H; Kur F; Beiras Fernandez A^*

来源：Transplantation Proceedings, 2014, 46(9): 3000-3003.

DOI：10.1016/j.transproceed.2014.07.016

Introduction. Antithymocyte globulin (ATG)-Fresenius (Neovii-Biotech, Graefelfing, Germany), a highly purified rabbit polyclonal antihuman T-lymphocyte immunoglobulin resulting from immunization of rabbits with the Jurkat T-lymphoblast cell line, is currently used for the prevention of acute rejection in patients receiving solid organ transplants. Our aim was to investigate the in vitro activity of ATG-Fresenius regarding the proliferation of peripheral blood mononuclear cells (PBMCs), an important mechanism of rejection after solid organ transplantation. %26lt;br%26gt;Methods. PBMCs were isolated from 6 healthy donors. Proliferation was assayed using [H-3] thymidine incorporation. For analysis of mitogen-stimulated proliferation, the PBMCs were incubated at 37 degrees C with various concentrations of ATG-Fresenius in the absence/presence of 40 mu g/mL phytohemagglutinin. For analysis of the mixed lymphocyte reaction, PBMCs were incubated at 37 degrees C with various concentrations of ATG-Fresenius for 3 days. On day 3, PBMCs (stimulator cells) from allogeneic donors were incubated with 25 mu g/mL mitomycin C. The responder cells (preincubated with ATG-Fresenius) were then cultured at 37 degrees C with the stimulator cells for 6 days. Groups were compared using ANOVA and the Tukey-Kramer multiple comparison test. %26lt;br%26gt;Results. Preincubation of PBMCs with ATG results in concentration-dependent inhibition of phytohemagglutinin-stimulated proliferation. The effect was more pronounced after 2 and 3 days of treatment with ATG compared with 1 day. There was a concentration-dependent decrease in the mixed lymphocyte reaction-induced proliferation (up to 80%) at ATG-Fresenius concentrations as low as 0.05 to 0.5 mu g/mL. No further effect on proliferation at ATG-Fresenius concentrations of 0.5 to 50 mu g/mL was seen, and higher concentrations (%26gt;100 mu g/mL) totally inhibited proliferation. %26lt;br%26gt;Conclusions. Our in vitro results provide more evidence of the beneficial effect of ATGs in the early phase of solid organ transplantation, by reducing effector cell proliferation.

• 出版日期2014-11