Interaction between B.7 and CD28 costimulatory molecules is essential for the activation of effector function...

The spontaneous regression of a rat histiocytoma, AK-5, is mediated by activated natural killer cells through antibody-dependent cellular cytotoxicity. In addition to the Fc-FcR interaction between the target and the effector cells demonstrated previously, we show the participation of costimulatory molecules B7 and CD28 in the efficient killing of the tumour cell. Blockade of the costimulatory interaction in vivo using anti-CD28 led to increased tumour growth and a suppressed cytokine response. Anti-CD28 antibody administration in vivo also diminished the cytotoxic potential of NK cells against AK-5 cells in vitro. Our studies also demonstrate the expression of B7.1 and B7.2 antigen on AK-5 tumour cells. The cytotoxic activity of natural killer cells was significantly inhibited when the effector/target cells were cultured in the presence of antibodies raised against B7.1, B7.2 and CD28. Administration of anti-CD28 in vivo also affected the efficiency of the formation of effector/target conjugates in vitro. Similarly, anti-CD28 injections affected expression of the adhesion molecules LFA 1 and ICAM 1 by splenocytes. Administration of anti-B7.1 and B7. 2 antibodies in AK-5 tumour-bearing animals showed a differential response. The cytotoxicity of natural killer cells was significantly inhibited after anti-B7.2 administration, suggesting the preferential participation of B7.2 molecules in vivo. These observations suggest an important role for B7-CD28 interaction in AK-5 tumour regression.