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 nonmalignant 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.
Koeppen
H K
HK
Department of Pathology, University of Chicago, Illinois 60637.
Singh
S
S
Stauss
H J
HJ
Park
B H
BH
Rowley
D A
DA
Schreiber
H
H
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000917:Antibody Formation; D000951:Antigens, Neoplasm / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016827:CD8 Antigens / Q000032:analysis; D005260:Female; D006084:Graft Rejection; D051379:Mice; D008815:Mice, Inbred Strains; D008819:Mice, Nude; D008822:Mice, Transgenic; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D016827:CD8 Antigens