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.
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5 January 1998
Article|
January 05 1998
Persistence of Peptide-induced CD4+ T cell Anergy In Vitro
Kelli R. Ryan,
Kelli R. Ryan
From the Department of Microbiology and Immunology, Emory University, Atlanta, Georgia 30322
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Brian D. Evavold
Brian D. Evavold
From the Department of Microbiology and Immunology, Emory University, Atlanta, Georgia 30322
Search for other works by this author on:
Kelli R. Ryan
From the Department of Microbiology and Immunology, Emory University, Atlanta, Georgia 30322
Brian D. Evavold
From the Department of Microbiology and Immunology, Emory University, Atlanta, Georgia 30322
Address correspondence to Dr. Brian D. Evavold, Department of Microbiology and Immunology, Emory University, 1510 Clifton Rd., Atlanta, GA 30322. Phone: 404-727-3393; FAX: 404-727-3659; E-mail: [email protected]
A portion of this paper was presented as a poster entitled “Long-term Maintenance of T Cell Anergy by a Peptide Analog” at the Keystone Symposia on Tolerance and Autoimmunity on 15 April 1997.
1
Abbreviation used in this paper: wt, wild-type.
Received:
August 19 1997
Revision Received:
October 24 1997
Online ISSN: 1540-9538
Print ISSN: 0022-1007
1998
J Exp Med (1998) 187 (1): 89–96.
Article history
Received:
August 19 1997
Revision Received:
October 24 1997
Citation
Kelli R. Ryan, Brian D. Evavold; Persistence of Peptide-induced CD4+ T cell Anergy In Vitro . J Exp Med 5 January 1998; 187 (1): 89–96. doi: https://doi.org/10.1084/jem.187.1.89
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