Persistence of Peptide-induced CD4+ T cell Anergy In Vitro
Open Access
- 5 January 1998
- journal article
- Published by Rockefeller University Press in The Journal of Experimental Medicine
- Vol. 187 (1) , 89-96
- https://doi.org/10.1084/jem.187.1.89
Abstract
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.Keywords
This publication has 39 references indexed in Scilit:
- The immune system evolved to discriminate infectious nonself from noninfectious selfPublished by Elsevier ,2003
- Partial activation of human T cells by peptide analogs on live APC: Induction of clonal anergy associated with protein tyrosine dephosphorylationHuman Immunology, 1997
- Structure of the p53 Tumor Suppressor Bound to the Ankyrin and SH3 Domains of 53BP2Science, 1996
- T Cell Activation Determined by T Cell Receptor Number and Tunable ThresholdsScience, 1996
- Serial triggering of many T-cell receptors by a few peptide–MHC complexesNature, 1995
- Partial T cell signaling: Altered phospho-? and lack of zap70 recruitment in APL-induced T cell anergyCell, 1994
- Tickling the TCR: selective T-cell functions stimulated by altered peptide ligandsImmunology Today, 1993
- Antigen analog-major histocompatibility complexes act as antagonists of the T cell receptorCell, 1992
- Separation of IL-4 Production from Th Cell Proliferation by an Altered T Cell Receptor LigandScience, 1991
- Split Anergy in a CD8 + T Cell: Receptor-dependent Cytolysis in the Absence of Interleukin-2 ProductionScience, 1991