T cell priming versus T cell tolerance induced by synthetic peptides.
It is well known that synthetic peptides are able to both induce and tolerize T cells. We have examined the parameters leading either to priming or tolerance of CD8+ cytotoxic T lymphocytes (CTL) in vivo with a major histocompatibility complex class I (H-2 Db) binding peptide derived from the glycoprotein (GP aa33-41) of lymphocytic choriomeningitis virus (LCMV). By varying dose, route, and frequency of LCMV GP peptide application, we found that a single local subcutaneous injection of 50-500 micrograms peptide emulsified in incomplete Freund's adjuvant protected mice against LCMV infection, whereas repetitive and systemic intraperitoneal application of the same dose caused tolerance of LCMV-specific CTL. The peptide-induced tolerance was transient in euthymic mice but permanent in thymectomized mice. These findings are relevant for a selective use of peptides as a therapeutic approach: peptide-induced priming of T cells for vaccination and peptide-mediated T cell tolerance for intervention in immunopathologies and autoimmune diseases.
Aichele
P
P
Institute of Experimental Immunology, University of Zürich, Switzerland.
Brduscha-Riem
K
K
Zinkernagel
R M
RM
Hengartner
H
H
Pircher
H
H
D000276:Adjuvants, Immunologic; D000818:Animals; D000956:Antigens, Viral / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D006023:Glycoproteins / Q000008:administration & dosage / Q000276:immunology*; D007108:Immune Tolerance; D007114:Immunization; D007115:Immunization Schedule; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D008213:Lymphocyte Activation; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009698:Nucleoproteins / Q000008:administration & dosage / Q000276:immunology*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000138:chemical synthesis / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000276:immunology; D013934:Thymectomy; D014764:Viral Proteins
D000276:Adjuvants, Immunologic; D000956:Antigens, Viral; D000939:Epitopes; D006023:Glycoproteins; D009698:Nucleoproteins; D010446:Peptide Fragments; D014764:Viral Proteins; C094244:glycoprotein peptide 33-41, Lymphocytic choriomeningitis virus; C094246:nucleoprotein peptide 118-126, lymphocytic choriomeningitis virus; C094245:nucleoprotein peptide 394-408, lymphocytic choriomeningitis virus