Peripheral immune tolerance blocks clonal expansion but fails to prevent the differentiation of Th1 cells.
Clonal anergy in Ag-specific CD4+ T cells is shown in these experiments to inhibit IL-2 production and clonal expansion in vivo. We also demonstrate that the defect in IL-2 gene inducibility can be achieved in both naive and Th1-like memory T cells when repeatedly exposed to aqueous peptide Ag. Nevertheless, this induction of clonal anergy did not interfere with the capacity of naive T cells to differentiate into Th1-like effector cells, nor did it prevent such helper cells from participating in T-dependent IgG2a anti-hapten responses and delayed-type hypersensitivity reactions. Thus, clonal anergy can contribute to the development of Ag-specific immune tolerance by limiting the size of a Th cell population, but not by disrupting its effector function.
Malvey
E N
EN
Department of Medicine, Center for Immunology, University of Minnesota Medical School, Minneapolis 55455, USA.
Jenkins
M K
MK
Mueller
D L
DL
D019264:Adoptive Transfer; D000818:Animals; D000941:Antigens / Q000008:administration & dosage / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D017635:Clonal Anergy / Q000235:genetics / Q000276:immunology*; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis; D016130:Immunophenotyping; D007275:Injections, Intravenous; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D007399:Interphase / Q000276:immunology; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000637:transplantation; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism
D000941:Antigens; D007074:Immunoglobulin G; D007376:Interleukin-2; C111390:OVA 323-339; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; D007371:Interferon-gamma; D010047:Ovalbumin