Defective T-cell receptor-induced apoptosis of T cells and rejection of transplanted immunogenic tumors in p53 -/- mice

Nagendra Singh, Lei Huang, Haiyan Qin

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Mice lacking the tumor suppressor gene p53 spontaneously develop T-cell lymphomas at a high rate, suggesting that in these mice lymphomas arise due to defective apoptosis mechanisms in T cells mediated by p53. However, a role of p53 in regulation of T-cell responses or apoptosis has been poorly defined. TCR-mediated signaling in the absence of CD28 costimulation induces both apoptosis and proliferation of na?̈ve T cells from WT mice. In this report we show that, in response to TCR stimulation, T cells from na?̈ve p53-deficient mice exhibited higher proliferation and drastically reduced apoptosis than WT T cells. CD28 costimulation enhanced the proliferation of TCR-stimulated WTand p53 -/- T cells, suggesting that p53 uncouples CD28-mediated antiapoptotic and proliferative signals. To evaluate the physiological significance of these findings, we transplanted OVA expressing-EG.7 tumor cells into WT and p53 -/- mice. Unlike WT mice, p53 -/- mice exhibited a robust tumor-resistant phenotype and developed cytotoxic T-cell responses against OVA. Collectively, these data support the hypothesis that p53 is an essential factor in negative regulation of T-cell responses and have implication for immunomodulation during treatment of cancers and other inflammatory conditions.

Original languageEnglish (US)
Pages (from-to)559-568
Number of pages10
JournalEuropean Journal of Immunology
Volume40
Issue number2
DOIs
StatePublished - Feb 1 2010

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T-Cell Antigen Receptor
Apoptosis
T-Lymphocytes
Neoplasms
Immunomodulation
T-Cell Lymphoma
Tumor Suppressor Genes
Lymphoma
Phenotype

Keywords

  • T-cell apoptosis and immune responses
  • p53

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Defective T-cell receptor-induced apoptosis of T cells and rejection of transplanted immunogenic tumors in p53 -/- mice . / Singh, Nagendra; Huang, Lei; Qin, Haiyan.

In: European Journal of Immunology, Vol. 40, No. 2, 01.02.2010, p. 559-568.

Research output: Contribution to journalArticle

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