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. J. Leukoc. Biol . 57: 462–468; 1995.