Abstract
Spontaneous cytotoxicity of human lymphocytes for tumours is increased by interferon (IFN) without change in the overall fraction of cells binding to targets. We developed an indirect immunofluorescent technique to stain lymphocytes conjugated to K-562 tumour cells in agarose with monoclonal antibodies. This allowed assessment of lymphocyte subpopulations binding to tumour cells without disruption of conjugates. Overall binding of non-adherent (NA) lymphocytes to tumour targets following incubation at 37 degrees C for 6 h was 13.3 +/- 0.3% compared to 12.5 +/- 0.7% with inclusion of IFN at 100 u/ml. When NA lymphocytes were incubated with K-562 tumour cells without IFN, OKM1 and OKT3 staining lymphocytes comprised 16.8 +/- 3.5% and 83.0 +/- 1.3% of the total lymphocyte population and 32.5 +/- 1.3% and 70.2 +/- 2.6% of lymphocytes conjugated to tumours. Incubation with IFN significantly increased OKM1 staining cells in the total NA population to 57.2 +/- 5.6% (P less than 0.01) and within tumour conjugates to 59.2 +/- 2.7% (P less than 0.01) while OKT3 staining cells decreased to 58.3 +/- 5.2% (P less than 0.02) and 45.3 +/- 1.2% (P less than 0.01), respectively. IFN increased cytotoxicity of NA cells for 51Cr-labelled K-562 by 66% at an effector to target ratio of 30:1 (P less than 0.001). These results demonstrate that OKM1 staining cells bind more avidly to tumour targets in the absence of IFN. IFN selectively increases the proportion of OKM1 staining lymphocytes with a concomitant increase in their binding to tumour cells. Therefore, enhancement of cytotoxicity by IFN in the NK system may result, in part, from conversion of OKT3 to OKM1 staining cells which are more efficient killers.
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