75-KDA 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 upregulated 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.