Bacterial superantigens as anti-tumour agents: induction of tumour cytotoxicity in human lymphocytes by staphylococcal enterotoxin A
- 46 Downloads
Activation of lymphocytes by interleukin-2 (IL-2) induces lymphokine-activated killer (LAK) cells that show promising effects on tumour growth in clinical trials. We examined the effect of the superantigen staphylococcal enterotoxin A (SEA) on anti-tumour activity of freshly prepared human lymphocytes. Picomolar amounts of SEA rapidly induced cytotoxic activity against K562 and Raji cells as well as some natural-killer(NK)-resistant tumour cell lines. Cytotoxic activity was not dependent on target cell expression of either major histocompatibility complex (MHC) class I or II antigens as shown using mutated cell lines. Cell-sorting experiments showed that the activity was expressed by NK (CD5−CD56+) as well as T (CD5+) cells, although the former contained the majority of cytotoxic activity. NK cells could not be directly activated by SEA. In contrast, SEA activated purified T cells to the same extent as in bulk cultures. It is suggested that SEA activation of NK cells is secondary to that brought about by lymphokines produced by T cells. Activation of LAK cells with SEA was comparable in magnitude as well as target cell spectrum to that of IL-2. In addition to the LAK-like cytotoxic activity induced by SEA, a superimposed cytotoxicity towards target cells expressing MHC class II antigens coated with SEA was observed. This staphylococcal-enterotoxin-dependent cell-mediated cytotoxicity (SDCC) was exclusively mediated by T cells. It is well established that MHC class II antigens function as receptors for staphylococcal enterotoxins on mammalian cells and that the complex between MHC class II antigen and — SEA apparently functions as a target structure for activated T cells with target cell lysis as a consequence. Activation of T lymphocytes with IL-2 also resulted in the capability to mediate SDCC. Staphylococcal enterotoxins represent a novel way of inducing anti-tumour activity in human lymphocytes, which could be of value in therapeutic applications.
Key wordsBacterial superantigens Antitumor agents Enterotoxin A Lymphocytes
Unable to display preview. Download preview PDF.
- 15.Henkart P, Martz E (eds) (1985) Mechanism of cell mediated cytotoxicity. Plenum, New York, p1Google Scholar
- 25.Mortarini R, Belli F, Parmiani G, Anichini A (1990) Cytokine-mediated modulation of HLA-Class II, ICAM-1, LFA-3 and tumour associated antigen profile of melanoma cells. Comparison with antiproliferative activity by rIL-1-beta, rTNF-alpha, rIFN-gamma, rIL-4 and their combinations. Int J Cancer 45: 334PubMedGoogle Scholar
- 27.Perlmann P, Cerottini JC (1979) Cytotoxic lymphocytes. In: Sela V (ed) The antigens. Academic Press, New York, p 173Google Scholar
- 31.Rosenberg SA, Lotze MT, Muul LM, Chang AE, Avis FP, Leitman S, Linehan WM, Robertsson CN, Lee RE, Rubin JT, Seipp CA, Simpson CG, White DE (1987) A progress report on the treatment of 157 patients with advanced cancer using lymphokine-activated killer cells and interleukin 2 or high-dose interleukin 2 alone. N Engl J Med 361: 889Google Scholar