75- but not 55-kDa tumor necrosis factor receptor is active in the homotypic aggregation and proliferation of human lymphokine-activated T killer (T-LAK) cells in vitro.
Lymphotoxin (LT) and tumor necrosis factor (TNF) play important roles in the maturation and growth of human lymphokine-activated T killer (T-LAK) cells in vitro. The role of 55- and 75-kDa TNF receptor (TNF-R) in the aggregation and proliferation of T-LAK cells was investigated using agonistic anti-TNF-R rabbit polyclonal antibodies. Human peripheral blood T cells and T-LAK cells predominantly express 75-kDa TNF-R. The proliferation of T-LAK cells during the generation phase is supported by innate LT and TNF. In this phase, the proliferation was upregulated by anti-75- but not 55-kDa TNF-R antibody. Homotypic aggregation of T-LAK cells was induced by LT, TNF, and anti-75- but not by anti-55-kDa TNF-R antibody. The increase of homotypic aggregation was accompanied by up-regulation of intercellular adhesion molecule 1 but not lymphocyte function-associated antigen 1 expression on cells and by an elevation of membrane fluidity, both of which were up-regulated by anti-75- but not 55-kDa TNF-R antibody. Interestingly, LT and TNF suppressed the proliferation of mature T-LAK cells. Anti-75- but not 55-kDa TNF-R antibody suppressed the proliferation, mimicking LT and TNF. These findings indicated that 75- but not 55-kDa TNF-R is biologically active in the modulation of aggregation and proliferation of human T-LAK cells in vitro.
Abe
Y
Y
Second Department of Surgery, Ehime University School of Medicine, Japan.
Yamauchi
K
K
Kimura
S
S
D002449:Cell Aggregation; D006801:Humans; D066298:In Vitro Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D015979:Killer Cells, Lymphokine-Activated / Q000166:cytology*; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D008233:Lymphotoxin-alpha / Q000494:pharmacology; D008560:Membrane Fluidity / Q000187:drug effects; D008970:Molecular Weight; D018124:Receptors, Tumor Necrosis Factor / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016169:Lymphocyte Function-Associated Antigen-1; D008233:Lymphotoxin-alpha; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1