Immortalized myeloid suppressor cells trigger apoptosis in antigen-activated T lymphocytes

E. Apolloni, V. Bronte, A. Mazzoni, P. Serafini, A. Cabrelle, D. M. Segal, H. A. Young, P. Zanovello

Research output: Contribution to journalArticle

125 Scopus citations

Abstract

We described a generalized suppression of CTL anamnestic responses that occurred in mice bearing large tumor nodules or immunized with powerful recombinant viral immunogens. Immune suppression entirely depended on GM-CSF-driven accumulation of CD11b+/Gr-1+ myeloid suppressor cells (MSC) in secondary lymphoid organs. To further investigate the nature and properties of MSC, we immortalized CD11b+/Gr-1+ cells isolated from the spleens of immunosuppressed mice, using a retrovirus encoding the v-myc and v-raf oncogenes. Immortalized cells expressed monocyte/macrophage markers (CD11b, F4/80, CD86, CD11c), but they differed from previously characterized macrophage lines in their capacities to inhibit T lymphocyte activation. Two MSC lines, MSC-1 and MSC-2, were selected based upon their abilities to inhibit Ag-specific proliferative and functional CTL responses. MSC-1 line was constitutively inhibitory, while suppressive functions of MSC-2 line were stimulated by exposure to the cytokine IL-4. Both MSC lines triggered the apoptotic cascade in Ag-activated T lymphocytes by a mechanism requiring cell-cell contact. Some well-known membrane molecules involved in the activation of apoptotic pathways (e.g., TNF-related apoptosis-inducing ligand, Fas ligand, TNF-α) were ruled out as candidate effectors for the suppression mechanism. The immortalized myeloid lines represent a novel, useful tool to shed light on the molecules involved in the differentiation of myeloid-related suppressors as well as in the inhibitory pathway they use to control T lymphocyte activation.

Original languageEnglish (US)
Pages (from-to)6723-6730
Number of pages8
JournalJournal of Immunology
Volume165
Issue number12
DOIs
StatePublished - Dec 15 2000
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Apolloni, E., Bronte, V., Mazzoni, A., Serafini, P., Cabrelle, A., Segal, D. M., Young, H. A., & Zanovello, P. (2000). Immortalized myeloid suppressor cells trigger apoptosis in antigen-activated T lymphocytes. Journal of Immunology, 165(12), 6723-6730. https://doi.org/10.4049/jimmunol.165.12.6723