Can the immunosupressive effect of perioperative single high-dose antithymocyte globulin administration in kidney allograft recipients be due to apoptosis of activated lymphocytes?

Treatment of Autoimmune Disease with Rabbit Anti‐T Lymphocyte Globulin

“…The bulk of rATG preparation is nonspecific rabbit IgG. The fraction of rATG that actually binds to cell‐surface ligands and receptors and imparts specific immunomodulatory signals is estimated at less than 0.5% of the total IgG mitogenic or superantigenic stimuli are seen at concentrations of <50 μg rATG/mL, 1,3 13 conversion of CD4 + CD25 − T cells to CD4 + CD25 + Foxp3 + T cells over a range of 7–60 μg rATG/mL 14 and apoptotic 2,4,5 and/or antiproliferative effect 1,13 over a range of 60–500 μg rATG/mL. The immunomodulatory effects of rATGs include the blockade of signals 1 and 2 of the T cell activation pathways, 12,15 inhibition of cellular adhesions, and lymphocyte migration in blood vessels during the period of ischemia reperfusion injury 16 …”

“…This is followed by complement-mediated lysis, 1-3 antibody-dependent cytotoxicity 1,2 or apoptosis. 4,5 The infusion of 2.5 mg thymoglobulin/kg bw triggers the release of Th2 cytokines; serum concentrations increase from three-to sixfold to a peak of 2,000-4,000 pg IL-6/mL and 1,000-1,500 pg TNF-␣/mL at 6 h. 6 After 24h intraoperative single high dosage infusion of 9 mg ATG-F/kg bw the mean serum concentrations increase from two-to threefold to 743 pg TNF-␣/mL and 26 pg IL-10/mL. 2,7 The levels of IL-10, IL-15, and IL-7 mRNA in peripheral blood lymphocytes are elevated from three-to fivefold at 24-48 h of ATG-F infusion.…”

“…Upon coating the plasma membrane of peripheral blood mononuclear cells (PBMCs) 1,2 or human autoreactive islet T cell line 3 with rATGs, a short‐term mitogenic or superantigenic effect is observed. This is followed by complement‐mediated lysis, 1–3 antibody‐dependent cytotoxicity 1,2 or apoptosis 4,5 . The infusion of 2.5 mg thymoglobulin/kg bw triggers the release of Th2 cytokines; serum concentrations increase from three‐ to sixfold to a peak of 2,000–4,000 pg IL‐6/mL and 1,000–1,500 pg TNF‐α/mL at 6 h 6 .…”