Enhancement of MHC-unrestricted cytotoxic activity of human CD56+ CD3- natural killer (NK) cells and CD3+ T cells by rhamnogalacturonan: target cell specificity and activity against NK-insensitive targets.
Rhamnogalacturonan-mediated enhancement of MHC-unrestricted cytotoxicity was studied with freshly isolated CD56+CD3- natural killer (NK) cells, interleukin-2 (IL-2)-activated CD56+ lymphokine-activated killer (LAK) cells und IL-2/anti-CD3-activated T cells as effector cells using NK-sensitive and NK-insensitive tumor cells as targets. The rhamnogalacturonan fractions IM, IP, and IQ were prepared from commercially available extracts of Viscum album. The dose/response relation of IM, IP, and IQ demonstrated the presence of various concentrations of cytotoxicity-enhancing compounds in all three fractions that were identified as rhamnogalacturonans by degradation studies with poly-alpha-D-galacturonidase (EC 3.2.1.15) and alpha-1,6-rhamnosidase (EC 3.2.1.40). Specific cytotoxicity of all three effector cell populations as well as the respective rhamnoagalacturonan-mediated cytotoxicity enhancement was readily inhibited in a dose-dependent manner by 60%-deacetylated mannose pentaacetate. Rhamnogalacturonan-mediated enhancement of cytotoxicity of fresh CD56+ NK cells was also observed with four of five NK-insensitive tumor cells as targets, indicating that the effector-cell/tumor-cell bridging activity of rhamnogalacturonans renders NK-insensitive targets susceptible to NK-mediated lysis. Moreover, the rhamnogalacturonan-mediated cytotoxicity enhancement became even more prominent when lymphokine-activated CD56+ LAK and CD3+ T cells were assayed with the NK-insensitive tumor cell targets.
Zhu
H G
HG
Friedrich-Miescher-Laboratorium, Max-Planck-Gesellscaft, Tübingen, Germany.
Zollner
T M
TM
Klein-Franke
A
A
Anderer
F A
FA
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D019002:CD56 Antigen; D003602:Cytotoxicity, Immunologic; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D008285:Major Histocompatibility Complex; D010368:Pectins / Q000494:pharmacology*; D011134:Polysaccharides / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000276:immunology*; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D019002:CD56 Antigen; D011134:Polysaccharides; D010368:Pectins