[Is it possible to treat diseases by manipulation of lymphocytes?].
Two signals are required for activation of T lymphocytes. Formation of tri-molecular complex among T cell antigen receptor(TCR), major histocompatibility complex(MHC) molecule, and antigen peptide produces signal 1 via TCR. Thus, signal 1 is antigen-dependent. However, signal 2 is elicited by interaction between CD28 and its ligands(CD80 and CD86) and is antigen-independent. Interestingly, cell surface expression of CD80 and CD86 on antigen-presenting cell(APC) is regulated by stimulus via CD40. In this review, it is shown that enhancement of signal 2 by agonistic anti-CD40 antibody increases immune responses, resulting in reinforcement of vaccine efficacy against influenza viruses and murine tumors, if antigen-dependent signal 1 is properly provided. In contrast, inhibition of signal 2 by anti-CD40 ligand(CD154) with pathogenic peptide K2 for EAU(experimental autoimmune uveoretinitis) tolerates T lymphocytes specific for K2, resulting in amelioration of EAU. Accordingly, herein, the possibility of application to humans for immunomanipulation with a controlled stimulus via CD40 is discussed.
Ogasawara
K
K
Second Department of Pathology, Shiga University of Medical Science, School of Medicine, Ohtsu 520-2192.
D000818:Animals; D000906:Antibodies / Q000502:physiology / Q000627:therapeutic use; D000938:Antigen-Presenting Cells / Q000276:immunology; D001327:Autoimmune Diseases / Q000628:therapy; D019013:CD40 Antigens / Q000276:immunology / Q000502:physiology; D023201:CD40 Ligand / Q000276:immunology; D019496:Cancer Vaccines; D003713:Dendritic Cells / Q000276:immunology; D006801:Humans; D007252:Influenza Vaccines; D008213:Lymphocyte Activation; D008285:Major Histocompatibility Complex / Q000502:physiology; D010455:Peptides / Q000502:physiology; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology*; D022223:Vaccines, Subunit
D000906:Antibodies; D019013:CD40 Antigens; D019496:Cancer Vaccines; D007252:Influenza Vaccines; D010455:Peptides; D011948:Receptors, Antigen, T-Cell; D022223:Vaccines, Subunit; D023201:CD40 Ligand