Suppression of various types of immune reactions including antibody (Ab) production, cell-mediated cytolysis (CMC), and delayed footpad reaction (DFR) was compared in EL-4 lymphoma-bearing syngeneic mice. In the primary response, the suppression of Ab production and CMC was detected 4 days after tumor inoculation, reached a peak on day 8, and then disappeared. The suppression of DFR was detected on day 1 and persisted to day 12. The suppressive effects of tumor-bearing mice could be transferred with sera to normal recipients, and the degree of the suppressive effect in tumor-bearing hosts correlated with the suppressive effect of sera but not with tumor size. In the secondary response, the suppressive effect of the tumor-bearing state was detected only on DFR. Spleen cells of these hosts were able to transfer positive DFR adoptively to normal recipients, indicating the presence of sensitized lymphocytes in the absence of expression. DFR of normal mice in the primary response was suppressed by transfer of sera of tumor-bearing mice befor elicitation, at which time sensitized lymphocytes should already have been raised. The very high susceptibility of DFR to the suppressive effects of the tumor-bearing state may be ascribed to the distinct susceptibility of mononuclear cells, probably of the macrophage series, which are required as secondary cells for expression of DFR. Further studies with Sephadex G-200 fractionation of the sera from the tumor-bearing mice showed that the immunosuppressive activity appeared in the initial fraction containing relatively high-molecular-weight materials.
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