In vitro comparison of two methods of T cell depletion associated with different rates of graft failure after allogeneic marrow transplantation.
Clinical trials in another center have shown a substantially lower risk of graft failure associated with T cell depletion by treatment of donor marrow with the use of an antibody against CD6 compared to depletion with a mixture of eight antibodies previously used for clinical trials in our center. In order to evaluate mechanisms possibly responsible for this difference, we compared lymphoid cell surface phenotypes and in vitro functions in marrow cells treated by complement-mediated lysis with anti-T12 (CD6) or with the eight antibody mixture. Treatment with the eight antibody mixture produced more than three log depletion of precursors for IL-2-producing cells (pIL-2) and approximately one log depletion of precursors for NK cells. On the other hand, treatment with anti-T12 produced approximately one log depletion of pIL-2 and had no effect on NK precursors. Additional studies were carried out with treated marrow cells cultured in medium containing recombinant IL-2. Compared to cells treated with the eight antibody mixture, the marrow cells that remained after anti-T12 treatment had more cytotoxic activity against K562, Daudi and an EBV-transformed human B cell line during the first 6 days of culture, but marrows treated by the two methods showed similar cytotoxic activity after 10 days of culture. Cultures from marrow treated with anti-T12 contained more CD3+ and CD6+ cells than cultures from marrow treated with the eight antibody mixture.(ABSTRACT TRUNCATED AT 250 WORDS)
Voltarelli
J C
JC
Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA 98104.
Corpuz
S
S
Martin
P J
PJ
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D001853:Bone Marrow / Q000473:pathology; D016026:Bone Marrow Transplantation / Q000379:methods*; D002478:Cells, Cultured; D003165:Complement System Proteins / Q000008:administration & dosage; D003601:Cytotoxicity Tests, Immunologic; D006084:Graft Rejection / Q000276:immunology; D006086:Graft vs Host Disease / Q000276:immunology; D006801:Humans; D008212:Lymphocyte Depletion; D013601:T-Lymphocytes / Q000276:immunology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; C062279:CD6 antigen; D003165:Complement System Proteins