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.
Raiter
A
A
Felsenstein Medical Research Center, Tel Aviv University, Sackler School of Medicine, Rabin Medical Center, Beilinson Campus, Petah-Tikva 49100, Israel.
Rodionov
G
G
Novogrodsky
A
A
Hardy
B
B
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D002051:Burkitt Lymphoma; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000276:immunology
D000911:Antibodies, Monoclonal; D016207:Cytokines; D015375:Receptors, Interleukin-2