Myeloid suppressor lines inhibit T cell responses by an NO-dependent mechanism

A. Mazzoni, V. Bronte, A. Visintin, J. H. Spitzer, E. Apolloni, P. Serafini, P. Zanovello, D. M. Segal

Research output: Contribution to journalArticle

426 Citations (Scopus)

Abstract

CD11b+ Gr-1+ myeloid suppressor cells (MSC) accumulate in lymphoid organs under conditions of intense immune stress where they inhibit T and B cell function. We recently described the generation of immortalized MSC lines that provide a homogeneous source of suppressor cells for dissecting the mechanism of suppression. In this study we show that the MSC lines potently block in vitro proliferation of T cells stimulated with either mitogen or antigenic peptide, with as few as 3% of MSC cells causing complete suppression. Inhibition of mitogenic and peptide-specific responses is not associated with a loss in IL-2 production or inability to up-modulate the early activation markers, CD69 and CD25, but results in direct impairment of the three IL-2R signaling pathways, as demonstrated by the lack of Janus kinase 3, STAT5, extracellular signal-regulated kinase, and Akt phosphorylation in response to IL-2. Suppression is mediated by and requires NO, which is secreted by MSC in response to signals from activated T cells, including IFN-γ and a contact-dependent stimulus. Experiments with inducible NO synthase knockout mice demonstrated that the inhibition of T cell proliferation by CD11b+Gr-1+ cells in the spleens of immunosuppressed mice is also dependent upon NO, indicating that the MSC lines accurately represent their normal counterparts. The distinctive capacity of MSC to generate suppressive signals when encountering activated T cells defines a specialized subset of myeloid cells that most likely serve a regulatory function during times of heightened immune activity.

Original languageEnglish
Pages (from-to)689-695
Number of pages7
JournalJournal of Immunology
Volume168
Issue number2
Publication statusPublished - Jan 15 2002

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Myeloid Cells
T-Lymphocytes
Cell Line
Interleukin-2
Janus Kinase 3
Peptides
Extracellular Signal-Regulated MAP Kinases
Mitogens
Knockout Mice
Nitric Oxide Synthase
B-Lymphocytes
Spleen
Phosphorylation
Cell Proliferation

ASJC Scopus subject areas

  • Immunology

Cite this

Mazzoni, A., Bronte, V., Visintin, A., Spitzer, J. H., Apolloni, E., Serafini, P., ... Segal, D. M. (2002). Myeloid suppressor lines inhibit T cell responses by an NO-dependent mechanism. Journal of Immunology, 168(2), 689-695.

Myeloid suppressor lines inhibit T cell responses by an NO-dependent mechanism. / Mazzoni, A.; Bronte, V.; Visintin, A.; Spitzer, J. H.; Apolloni, E.; Serafini, P.; Zanovello, P.; Segal, D. M.

In: Journal of Immunology, Vol. 168, No. 2, 15.01.2002, p. 689-695.

Research output: Contribution to journalArticle

Mazzoni, A, Bronte, V, Visintin, A, Spitzer, JH, Apolloni, E, Serafini, P, Zanovello, P & Segal, DM 2002, 'Myeloid suppressor lines inhibit T cell responses by an NO-dependent mechanism', Journal of Immunology, vol. 168, no. 2, pp. 689-695.
Mazzoni A, Bronte V, Visintin A, Spitzer JH, Apolloni E, Serafini P et al. Myeloid suppressor lines inhibit T cell responses by an NO-dependent mechanism. Journal of Immunology. 2002 Jan 15;168(2):689-695.
Mazzoni, A. ; Bronte, V. ; Visintin, A. ; Spitzer, J. H. ; Apolloni, E. ; Serafini, P. ; Zanovello, P. ; Segal, D. M. / Myeloid suppressor lines inhibit T cell responses by an NO-dependent mechanism. In: Journal of Immunology. 2002 ; Vol. 168, No. 2. pp. 689-695.
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