Mechanism of tumor rejection in anti-CD3 monoclonal antibody-treated mice.
The present study was undertaken to determine the mechanism of tumor rejection in mice treated with low dose anti-CD3 mAb. It was found that treated mice developed nonrestricted antitumor cytolytic spleen cells of the Thy-1+, asialo GM-1+, CD4-, CD8- phenotype. Although these cells might play a role in immunopotentiating some immune responses, in vivo depletion studies using anti-asialo GM-1 mAb demonstrated that these cells were not involved in the rejection of the progressor tumor, 1591-PRO4L, by anti-CD3 mAb-treated mice. Mice treated with anti-CD3 did develop lasting tumor specific immunity as demonstrated by their ability to reject PRO4L on tumor rechallenge while being unable to reject an unrelated UV-induced tumor. The specificity of this memory implicated T cells in the response to PRO4L in anti-CD3-treated mice. Using in vivo T cell subset depletion of anti-CD3-treated animals, it was shown that both CD4+ and CD8+ T cells are required for anti-CD3-induced tumor rejection. The CD4+ cells provide helper function and are only required in the early rejection period, whereas CD8+ cells are required throughout the immune response. In fact, examination of rejecting tumors from treated animals revealed the presence of tumor-specific CD8+ cytolytic T cells capable of cytolysis immediately after removal from the rejecting PRO4L tumor. Thus, in vivo treatment with anti-CD3 mAb likely results in the pan-stimulation of the entire T cell population, which enhances the generation of specific CD8+ T cells, which then eliminate the tumor.
Ellenhorn
J D
JD
University of Chicago, Ben May Institute, Department of Pathology, Chicago, IL.
Schreiber
H
H
Bluestone
J A
JA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis / Q000502:physiology*; D017252:CD3 Complex; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016827:CD8 Antigens; D004306:Dose-Response Relationship, Immunologic; D007116:Immunization, Passive; D007167:Immunotherapy; D008213:Lymphocyte Activation; D051379:Mice; D008809:Mice, Inbred C3H; D009374:Neoplasms, Experimental / Q000276:immunology / Q000628:therapy*; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D016827:CD8 Antigens; D011948:Receptors, Antigen, T-Cell