Natural and reinforced immunity against hapten-modified cells in vivo: importance of serum-borne and cellular factors.

Chromium 51-labelled murine splenocytes were injected intravenously into syngeneic non-immune recipients. The percentages of radioactivity recovered in the spleens and the livers were determined, together with the liver/spleen (L/S) radioactivity ratios. It was found that using trinitrobenzene sulphonate (TNBS)-treated cells resulted in a diminution of splenic recovery, with a concomitant augmentation of the L/S ratio, which corresponded to figures found when non-treated xenogeneic lymphocytes were injected. When using splenocytes modified with trifluoromethyl-dinitrobenzene sulphonate (CF3-DNBS)--an analogue of TNBS--this sort of natural immunity was not observed. As cell modifications with TNBS and CF3-DNBS have previously been shown to cross-react in purely cellular immunity tests, the striking difference observed here was tentatively attributed to differential sensitivity to serum-borne factors which mediate this in vivo natural resistance. These factors are likely to be naturally occurring anti-trinitrophenyl antibodies. Contrastingly, if TNBS- and CF3-DNBS-modified splenocytes were injected into either anti-TNBS or anti-CF3-DNBS immunized mice, the modification of radioactivity recovery and L/S indexes (compared to those in non-immunized controls) was always greater in the case of the CF3-DNBS cells. It is concluded that, of these two cross-reacting cell surface modifying treatments, one (TNBS) is sensitive both to natural and reinforced immunity, whereas the second (CF3-DNBS) is sensitive only to reinforced immunity. As we have previously shown in vitro, that CF3-DNBS-modified cells do not seem to be sensitive to cytotoxic antibodies, we believe that the in vivo immune rejection observed is essentially a cell-mediated reaction, whereas the natural immunity is mainly a serum-dependent reaction.