DEPRESSION BY ANTIBODY OF THE IMMUNE RESPONSE TO HOMOGRAFTS AND ITS ROLE IN IMMUNOLOGICAL ENHANCEMENT

Abstract

This paper reports tests of two hypotheses that have been proposed to account for the enhanced growth of tumor homografts in the presence of antiserum reactive with the graft (immunological enhancement). According to the first hypothesis, enhancement is due to some "physiological" alteration in the tumor, induced by its contact with antiserum, which insures its survival despite the hostile response of the host. According to the second hypothesis, antiserum alters the response of the host. By blocking the development of the cellular type of immunity, which is the main agent in graft destruction, it permits the graft to survive. To test hypothesis 1, strain A tumor SaI was passed from A's, and from enhanced B10.D2's, into untreated B10.D2's. The per cent of deaths was essentially the same in both groups (48 and 44 per cent, respectively); there was no evidence that passage through enhanced B10.D2's altered the capacity of the tumor to grow in the foreign strain. Several other groups of mice included in the experiment all confirmed this conclusion. The experiment failed to confirm hypothesis 1. In the tests of hypothesis 2, the effect of isoantiserum on immune responses of both the humoral and cellular type was measured. When antiserum was given together with foreign strain lymphoid cells (antigen), almost no additional antibody was manufactured; in contrast with this, controls receiving foreign cells only produced red cell agglutinating antibody in high titer. The effect of antiserum on the development of immunity of the cellular type was tested by the method of Winn. In this assay, presumptively immune node cells, in various dilutions, are mixed with tumor cells and injected into appropriate mice. Immunity is indicated by inhibited tumor growth. Antiserum given at the same time as a tumor homograft greatly depressed the immunity of the cells expressed from the draining nodes. At 6 days after the graft, the level of immunity of cells from treated mice was 1/24th to 1/32nd that of cells from controls receiving tumor alone. The same sort of depressing effect was noted when the immunizing tissue was foreign thymus or embryo. Antiserum given 1 or more days after the immunizing tissue also resulted in a lower level of cellular immunity (but the assay used in this case was a less critical one). These results provide an adequate explanation of the phenomenon of immunological enhancement, at least as it occurs in the particular test system used in these experiments. Since it is cellular immunity rather than humoral antibody that inhibits the growth of most grafts (transplantable leukemias are an exception), the depression of this immunity by antibody is favorable to the growth of a homograft.