Open AccessInduction of cytotoxicity in resting human T lymphocytes bound to tumor cells by antibody heteroconjugates.
Author(s) -
Gundram Jung,
Jeffrey A. Ledbetter,
Hans J. MüllerEberhard
Publication year - 1987
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.84.13.4611
Subject(s) - peripheral blood mononuclear cell , cytotoxic t cell , monoclonal antibody , antibody , microbiology and biotechnology , cytotoxicity , biology , cd28 , immunology , lymphocyte , t cell , t lymphocyte , antigen , in vitro , chemistry , cd8 , immune system , biochemistry
An in vitro model for peripheral human T-cell activation and resultant tumor cell killing is described. Cytotoxic T lymphocytes may be generated from resting lymphocytes by incubation of human peripheral blood mononuclear cells for 3 days with the anti-CD3 monoclonal antibody OKT3. Cytotoxicity in peripheral blood mononuclear cells can also be induced by adding an anti-target-OKT3 antibody conjugate and 10% (vol/vol) fetal calf serum to the culture medium. Conjugate activation of T cells was almost completely blocked, however, when 20% (vol/vol) human serum was added to the medium. Conjugate-mediated peripheral blood mononuclear cells activation was restored to some extent by the addition of melanoma target cells to the culture and was markedly enhanced by a second conjugate containing anti-target cell and anti-CD28 antibody. Monoclonal antibody 9.3 (anti-CD28) provides a progression signal in T-lymphocyte activation when used in combination with anti-CD3. Thus, presentation by the tumor target cells of anti-CD3 and anti-CD28 to resting human lymphocytes causes T-cell activation, which is independent of monocytes, proceeds in the presence of human serum, and results in tumor cell killing.