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

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-? have been studied individually, the influence of CD8 co-receptor on TGF-? function in CD8+ T cells is unknown. Here, we show that while CD8 enhances T cell activation, it also enhances susceptibility to TGF-?-mediated immune suppression. Using Jurkat cells expressing a full-length, truncated or no ??CD8 molecule, we demonstrate that cells expressing full-length ??CD8 were highly susceptible, ??CD8-truncated cells were partially susceptible, and CD8-deficient cells were completely resistant to suppression by TGF-?. Additionally, we determined that inhibition of Lck rendered mouse CD8+ T cells highly resistant to TGF-? suppression. Resistance was not associated with TGF-? 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-?. Based on the important role which TGF-?-mediated suppression plays in tumor immunology, these findings unveil necessary considerations in formulation of CD8+ T cell-related cancer immunotherapy strategies.

SUBMITTER: Zloza A

PROVIDER: S-EPMC4507403 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature

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

Zloza Andrew A Jagoda Michael C MC Lyons Gretchen E GE Graves Michael C MC Kohlhapp Frederick J FJ O'Sullivan Jeremy A JA Lacek Andrew T AT Nishimura Michael I MI Guevara-Patiño José A JA

Cancer immunology, immunotherapy : CII 20101231 2

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, ...[more]

PMID: 21193909

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Dataset Information

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

Publications

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

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