CD8 co-receptor promotes susceptibility of CD8+ T cells to transforming growth factor-β (TGF-β)-mediated suppression

Andrew Zloza, Michael C. Jagoda, Gretchen E. Lyons, Michael C. Graves, Frederick J. Kohlhapp, Jeremy A. O'Sullivan, Andrew T. Lacek, Michael I. Nishimura, José A. Guevara-Patiño

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

CD8+ T cell function depends on a finely orchestrated balance of activation/suppression signals. While the stimulatory role of the CD8 co-receptor and pleiotropic capabilities of TGF-β have been studied individually, the influence of CD8 co-receptor on TGF-β function in CD8+ T cells is unknown. Here, we show that while CD8 enhances T cell activation, it also enhances susceptibility to TGF-β-mediated immune suppression. Using Jurkat cells expressing a full-length, truncated or no αβCD8 molecule, we demonstrate that cells expressing full-length αβCD8 were highly susceptible, αβCD8-truncated cells were partially susceptible, and CD8-deficient cells were completely resistant to suppression by TGF-β. Additionally, we determined that inhibition of Lck rendered mouse CD8+ T cells highly resistant to TGF-β suppression. Resistance was not associated with TGF-β receptor expression but did correlate with decreased Smad3 and increased Smad7 levels. These findings highlight a previously unrecognized third role for CD8 co-receptor which appears to prepare activated CD8+ T cells for response to TGF-β. Based on the important role which TGF-β-mediated suppression plays in tumor immunology, these findings unveil necessary considerations in formulation of CD8+ T cell-related cancer immunotherapy strategies.

Original languageEnglish (US)
Pages (from-to)291-297
Number of pages7
JournalCancer Immunology, Immunotherapy
Volume60
Issue number2
DOIs
StatePublished - Feb 2011

Keywords

  • CD8 T cells
  • CD8 co-receptor
  • Lck
  • SMADs
  • TGF-β
  • Tumor-induced suppression

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Cancer Research

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    Zloza, A., Jagoda, M. C., Lyons, G. E., Graves, M. C., Kohlhapp, F. J., O'Sullivan, J. A., Lacek, A. T., Nishimura, M. I., & Guevara-Patiño, J. A. (2011). CD8 co-receptor promotes susceptibility of CD8+ T cells to transforming growth factor-β (TGF-β)-mediated suppression. Cancer Immunology, Immunotherapy, 60(2), 291-297. https://doi.org/10.1007/s00262-010-0962-6