Clonal anergy is maintained independently of T cell proliferation

Sara Colombetti, Fabio Benigni, Veronica Basso, Anna Mondino

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Ag encounter in the absence of proliferation results in the establishment of T cell unresponsiveness, also known as T cell clonal anergy. Anergic T cells fail to proliferate upon restimulation because of the inability to produce IL-2 and to properly regulate the G1 cell cycle checkpoint. Because optimal TCR and CD28 engagement can elicit IL-2-independent cell cycle progression, we investigated whether CD3/CD28-mediated activation of anergic T cells could overcome G1 cell cycle block, drive T cell proliferation, and thus reverse clonal anergy. We show here that although antigenic stimulation fails to elicit G1-to-S transition, anti-CD3/CD28 mAbs allow proper cell cycle progression and proliferation of anergic T cells. However, CD3/CD28-mediated cell division does not restore Ag responsiveness. Our data instead indicate that reversal of clonal anergy specifically requires an IL-2-dependent, rapamycin-sensitive signal, which is delivered independently of cell proliferation. Thus, by tracing proliferation and Ag responsiveness of individual cells, we show that whereas both TCR/CD28 and IL-2-generated signals can drive T cell proliferation, only IL-2/IL-2R interaction regulates Ag responsiveness, indicating that proliferation and clonal anergy can be independently regulated.

Original languageEnglish
Pages (from-to)6178-6186
Number of pages9
JournalJournal of Immunology
Volume169
Issue number11
Publication statusPublished - Dec 1 2002

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Clonal Anergy
Cell Proliferation
T-Lymphocytes
Interleukin-2
Cell Cycle
G1 Phase Cell Cycle Checkpoints
Sirolimus
Cell Division

ASJC Scopus subject areas

  • Immunology

Cite this

Colombetti, S., Benigni, F., Basso, V., & Mondino, A. (2002). Clonal anergy is maintained independently of T cell proliferation. Journal of Immunology, 169(11), 6178-6186.

Clonal anergy is maintained independently of T cell proliferation. / Colombetti, Sara; Benigni, Fabio; Basso, Veronica; Mondino, Anna.

In: Journal of Immunology, Vol. 169, No. 11, 01.12.2002, p. 6178-6186.

Research output: Contribution to journalArticle

Colombetti, S, Benigni, F, Basso, V & Mondino, A 2002, 'Clonal anergy is maintained independently of T cell proliferation', Journal of Immunology, vol. 169, no. 11, pp. 6178-6186.
Colombetti S, Benigni F, Basso V, Mondino A. Clonal anergy is maintained independently of T cell proliferation. Journal of Immunology. 2002 Dec 1;169(11):6178-6186.
Colombetti, Sara ; Benigni, Fabio ; Basso, Veronica ; Mondino, Anna. / Clonal anergy is maintained independently of T cell proliferation. In: Journal of Immunology. 2002 ; Vol. 169, No. 11. pp. 6178-6186.
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