Rabbit anti T-lymphocyte globulin induces apoptosis in peripheral blood mononuclear cell compartments and leukemia cells, while hematopoetic stem cells are apoptosis resistant.
Polyclonal anti-T-lymphocyte globulins (ATG) are used in allogeneic stem cell transplantation (SCT) for the prophylaxis of graft versus host disease (GVHD) by in vivo T cell depletion. In this study we investigated the complement independent induction of apoptosis by rabbit ATG in peripheral blood mononuclear cell (PBMNC) compartments and hematopoetic stem cells (HSC). We also detected antileukemic activity of ATG by measuring apoptosis in myeloid and lymphatic leukemia cell lines and primary leukemia cells. We found ATG to induce apoptosis in T-lymphocytes (CD4(+), CD8+), B-lymphocytes (CD20+), natural killer (NK)-cells (CD56(+)), and monocytes (CD14(+)). HSC, in contrast, were apoptosis resistant and could be growth stimulated by low-dose ATG in the presence of bystander cells. The human leukemia cell lines Jurkat, Daudi, DG-75 (lymphoblastic), and K562, HL-60, KG1, and U937 (myeloblastic) underwent ATG-induced apoptosis, whereas the NK-cell line YT was resistant. Primary leukemia cells from 6 investigated patients with acute lymphoblastic leukemia, 9 of 10 patients with chronic lymphocytic leukemia, and 4 of 8 patients with acute myeloblastic leukemia underwent ATG-induced apoptosis. We conclude apoptosis induction in all PBMNC compartments contributes to GVHD prophylaxis. ATG might support engraftment. Finally, antileukemic activity of ATG could positively influence the transplantation outcome.
Grüllich
Carsten
C
Albert Ludwigs-University Medical Center Freiburg, Department of Hematology and Oncology, Freiburg, Germany. carsten.gruellich@nct-heidelberg.de
Ziegler
Christian
C
Finke
Jürgen
J
D000818:Animals; D000961:Antilymphocyte Serum / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D001402:B-Lymphocytes; D002478:Cells, Cultured; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000517:prevention & control*; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D007938:Leukemia / Q000473:pathology*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell; D015470:Leukemia, Myeloid, Acute; D007963:Leukocytes, Mononuclear / Q000166:cytology*; D009000:Monocytes; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma; D011817:Rabbits; D013601:T-Lymphocytes
D000961:Antilymphocyte Serum