Persistence of peptide-induced CD4+ T cell anergy in vitro.
Clonal T cell unresponsiveness, or anergy, has been proposed as a mechanism of peripheral tolerance in vivo, and as a potential means of curbing unwanted T cell responses. In this study, anergy was induced in a T helper cell (Th) clone reactive to hemoglobin (Hb) peptide 64-76 by coculture of the T cells with live antigen-presenting cells (APCs) and 74L, a peptide analog of Hb(64-76) that contains a single amino acid substitution of leucine for glycine at position 74, or with a low concentration of the agonist ligand. The anergic state was characterized by blunted proliferation and interleukin (IL) 2 production upon restimulation with Hb(64-76), and was not the result of impaired TCR/CD3 downmodulation. The addition of exogenous IL-12 transiently restored proliferation of the anergic lines, but removal of IL-12 from culture returned the T cells to their nonproliferative state. Interestingly, persistence of the anergic phenotype was observed despite biweekly restimulation with antigen, APCs, and IL-2. Thus, T cell unresponsiveness induced by a peptide produced a stable, persistent anergic state in a Th0 clone that was not reversible by stimulation with IL-2 or -12.
Ryan
K R
KR
Department of Microbiology and Immunology, Emory University, Atlanta, Georgia 30322, USA.
Evavold
B D
BD
D000595:Amino Acid Sequence; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D017635:Clonal Anergy; D015536:Down-Regulation; D006454:Hemoglobins / Q000235:genetics / Q000276:immunology; D066298:In Vitro Techniques; D018664:Interleukin-12 / Q000494:pharmacology; D007376:Interleukin-2 / Q000096:biosynthesis / Q000494:pharmacology; D008213:Lymphocyte Activation; D051379:Mice; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology; D010455:Peptides / Q000276:immunology*; D010641:Phenotype; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000378:metabolism
D006454:Hemoglobins; D007376:Interleukin-2; D010446:Peptide Fragments; D010455:Peptides; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D018664:Interleukin-12