CD3zeta expression and T cell proliferation are inhibited by TGF-beta1 and IL-10 in cervical cancer patients

J Clin Immunol. 2009 Jul;29(4):532-44. doi: 10.1007/s10875-009-9279-7. Epub 2009 Mar 4.

Abstract

Introduction: Cervical cancer development from a squamous intraepithelial lesion is thought to be favored by an impaired T cell immunity. We evaluated parameters of T cell alterations such as proliferation, cytokine, and CD3zeta expression in peripheral blood and tumor-infiltrating T lymphocytes from women with squamous intraepithelial lesions (SIL) or cervical cancer (CC).

Results and discussion: T cell proliferation and cytokine messenger RNA (mRNA) expression were similar in women with SIL and healthy donors, whereas low T cell proliferation and lower mRNA expression of IL-2, IL-10 and IFN-gamma were observed in women with CC. Moreover, infiltrating cells showed marginal responses. We also found that CD3zeta mRNA expression, whose protein is required for T cell activation, correlated with a decreased proliferation in advanced stages of the disease.

Conclusion: Experiments with T cells from healthy donors in the presence TGF-beta1 or IL-10 suggest that these cytokines have a relevant role in T cell responses during CC progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • CD3 Complex / biosynthesis*
  • CD3 Complex / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Culture Media, Conditioned / pharmacology
  • Female
  • HeLa Cells
  • Humans
  • Interferon-gamma / immunology
  • Interferon-gamma / metabolism
  • Interleukin-10 / immunology*
  • Interleukin-10 / pharmacology
  • Interleukin-2 / immunology
  • Lymphocytes, Tumor-Infiltrating / drug effects
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Middle Aged
  • Phytohemagglutinins / pharmacology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*
  • Transforming Growth Factor beta1 / immunology*
  • Transforming Growth Factor beta1 / pharmacology
  • Uterine Cervical Dysplasia / immunology*
  • Uterine Cervical Dysplasia / pathology
  • Uterine Cervical Neoplasms / immunology*
  • Uterine Cervical Neoplasms / pathology

Substances

  • CD3 Complex
  • CD3 antigen, zeta chain
  • Culture Media, Conditioned
  • IL10 protein, human
  • IL2 protein, human
  • Interleukin-2
  • Phytohemagglutinins
  • Transforming Growth Factor beta1
  • Interleukin-10
  • Interferon-gamma