Cytokine-induced killer cells against autologous CLL: direct cytotoxic effects and induction of immune accessory molecules by interferon-gamma.
Cytokine-induced killer cells (CIK cells), coexpressing CD3 and CD56, can be expanded from peripheral blood mononuclear cells by the timed addition of interferon-gamma (IFN-gamma), IL-2 and OKT3. The effects of CIK cells on primary, autologous CLL cells are described. We used MACS to separate CD3(+) cells for expansion of CIK cell effectors and CD19(+) targets from peripheral blood of 16 CLL patients. Apoptosis was assessed by measuring annexinV staining in CLL cells. After incubation of autologous CIK with CLL, specific apoptosis in CLL cells was 15%. Coincubation with irradiated CIK cells for 48 hr before adding vital CIK cells resulted in an increased ICAM-1 expression on CLL cells and an increase in apoptosis of CLL targets (30%). These effects were mediated by IFN-gamma secretion of CIK cells. In addition to their direct cytotoxic effect, CIK cells secrete IFN-gamma that modulates the expression of adhesion molecules on CLL cells, and this enhances apoptosis induction by cytotoxic effector cells.
Kornacker
Martin
M
Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany. martin_kornacker@med.uni-heidelberg.de
Moldenhauer
Gerhard
G
Herbst
Markus
M
Weilguni
Edeltraud
E
Tita-Nwa
Freddy
F
Harter
Christoph
C
Hensel
Manfred
M
Ho
Anthony D
AD
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000276:immunology*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology* / Q000628:therapy; D007963:Leukocytes, Mononuclear; D051379:Mice; D008875:Middle Aged; D016853:Muromonab-CD3 / Q000494:pharmacology*; D041681:NIH 3T3 Cells; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D016853:Muromonab-CD3; D011994:Recombinant Proteins; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma