CD4+ T lymphocytes as a primary cellular target for BAT mAb stimulation.

BAT is a monoclonal antibody (mAb) produced against membranes of a human Burkitt lymphoma cell line (Daudi) that was selected for its ability to stimulate lymphocyte proliferation. BAT manifests anti-tumor properties in mice bearing a variety of murine tumors. BAT also induced regression of human tumors inoculated into SCID mice that had been engrafted with human lymphocytes. The anti-tumor activity of BAT was related to its immune stimulatory properties. Previous data indicated that T lymphocytes and NK cells mediate in vivo the anti-tumor activity. In order to define the primary target cell for BAT stimulatory activity, the in vitro stimulatory effect of BAT on purified lymphocyte subpopulations was investigated. Human CD4(+), CD8(+) T cells and CD56(+) NK cells were purified and their in vitro response to BAT was investigated. Results indicate that BAT selectively stimulated CD4(+) cells as assessed by proliferation and secretion of IFN-gamma. FACS analysis has also revealed a selective increase in BAT antigen on CD4(+) T cells that were cultured with BAT antibody. The effector cells that mediate BAT-induced tumor eradication may, however, be distinct from those that serve as the primary cellular target of the antibody. Cytokines such as IFN-gamma that are produced by CD4(+) cells may be involved in activation of additional cell types that may be involved in tumor destruction.