CD4-positive and B lymphocytes in transplantation immunity: I. Promotion of tumor allograft rejection through elimination of CD4-positive lymphocytes

The elimination of CD4⁺ cells by anti-CD4 antibody caused regression of a malignant solid tumor allograft that does not lose a cytotoxic T lymphocyte—defined target antigen during tumor progression and requires specific CD8⁺ CTL for tumor rejection. Treatment with anti-CD4 antibody was effective when started 1-2 weeks after tumor challenge and was at least as effective as treating with anti-CD3 antibody or specific immunization with the antigen expressed on malignant or non-malignant cells. None of these treatments caused rejection of tumors that were larger than 1 cm³ or had been growing for 3 weeks or longer in the host. Mice bearing large and long-established tumors treated with anti-CD4 antibody rejected a new tumor challenge but failed to reject the long-established tumor. Similarly, mice with established tumors mounted effective CTL responses to reject skin grafts but failed to reject tumors which expressed the same antigen. Treatment with anti-CD4 antibody eliminated primary T lymphocyte dependent antibody responses but failed to suppress ongoing antibody responses to continuous antigenic stimulation. Possibly, the effectiveness of early treatment and the failure of later treatment with anti-CD4 antibody results indirectly from the effect treatment has on B lymphocytes.