Enhancement of the TCRζ expression, polyclonal expansion, and activation of t cells from patients with acute myeloid leukemia after IL-2, IL-7, and IL-12 induction

DNA Cell Biol. 2015 Jul;34(7):481-8. doi: 10.1089/dna.2015.2810. Epub 2015 Mar 10.

Abstract

Defective T cell receptor (TCR) signaling resulting in lower T cell function plays a crucial role in the pathogenesis of T cell immunodeficiency in leukemia. Previous studies have indicated that lower TCRζ levels are a common characteristic of patients with leukemia, and upregulating TCRζ could partially recover T cell function. In this study, we characterized the effect of the stimulating factor induction on the TCRζ, Zap-70, and FcɛRIγ levels, IFN-γ secretion, and the distribution and clonal expansion of TCR Vβ subfamilies in CD3(+) T cells sorted from peripheral blood from acute myeloid leukemia (AML) patients. The induction included single stimulating factor or a combination with different cytokines (IL-2, IL-7, IL-2+IL-7, IL-7+IL-12, CD3, CD3+CD28 antibody, CD3+CD28 antibody+IL-2, and CD3+CD28 antibody+IL-7) at 72 h. The results showed that increased TCRζ and Zap-70 levels with deceased FcɛRIγ in T cells after induction, and different responses to cytokine in T cell from different cases may indicate the heterogeneity of T cells and different immune statuses in different AML cases. Increased IFN-γ levels in T cells from AML patients were detected after induction in the IL-12+IL-7, CD3+CD28+IL-2, and CD3+CD28+IL-7 groups. Moreover, the number of TCR Vβ subfamily T cells expressed was increased; however, all of the TCR Vβ subfamily T cells in the AML patients could not be completely recovered after induction. In conclusion, the cytotoxicity and activation function of T cells could be enhanced after induction by different stimuli accompanied by an increase in TCRζ and Zap-70 and recovery of the TCR Vβ repertoire in AML patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Cell Proliferation
  • Cells, Cultured
  • Female
  • Humans
  • Interferon-gamma / metabolism
  • Interleukin-12 / pharmacology*
  • Interleukin-2 / pharmacology*
  • Interleukin-7 / pharmacology*
  • Leukemia, Myeloid, Acute / immunology*
  • Leukemia, Myeloid, Acute / metabolism
  • Lymphocyte Activation
  • Male
  • Middle Aged
  • Receptors, Antigen, T-Cell / metabolism*
  • Receptors, IgE / metabolism
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • Young Adult
  • ZAP-70 Protein-Tyrosine Kinase / metabolism

Substances

  • Interleukin-2
  • Interleukin-7
  • Receptors, Antigen, T-Cell
  • Receptors, IgE
  • antigen T cell receptor, zeta chain
  • Interleukin-12
  • Interferon-gamma
  • ZAP-70 Protein-Tyrosine Kinase