Selective inhibition of T lymphocyte repopulation of lymphoid organs as a mechanism of immunosuppression in tumor-bearing mice.

Abstract

The mechanism of selective suppression of T-cell activity in Ehrlich tumor-bearing mice was investigated in an adoptive cell transfer system of secondary antibody responses to haptens. The induction of secondary antidinitrophenyl (DNP) antibody response after stimulation with DNP-homologous carrier (TD) of thymus-dependent DNP-carrier (TD)-primed spleen cells was markedly inhibited in tumor-bearing recipient mice, whereas the response to thymus independent DNP-carrier (TID) was intact as compared to that seen in normal recipients. However, if tumors were induced in the DNP-TD-primed donor mice and the spleen cells were assayed for responsiveness to DNP-TD in normal recipients, they generated a normal anti-hapten antibody response. After the DNP-TD-primed cells had been transferred into normal recipients and tumors had been induced in the recipients before DNP-TD-stimulation, the cells in tumor-bearers responded normally. These results indicate that the tumor-bearing state neither directly suppresses the responsiveness of primed cells nor interferes with the mechanism for antigen stimulation of primed cells. Direct measurement of recovery of transferred primed T and B cells from the spleen of tumor-bearing recipients revealed that the net recovery of T-cell activity markedly decreased, whereas the recovery of B cells in the spleens of tumor-bearing hosts was not affected or was even higher than the normal. Prevention of repopulation by T lymphocytes of lymphoid organs due to a postulated change in the microenvironment is suggested as a mechanism for the selective suppression of T-cell activity in Ehrlich tumor-bearing animals.