Zinc Ionophore Pyrithione Mimics CD28 Costimulatory Signal in CD3 Activated T Cells

Int J Mol Sci. 2024 Apr 12;25(8):4302. doi: 10.3390/ijms25084302.

Abstract

Zinc is an essential trace element that plays a crucial role in T cell immunity. During T cell activation, zinc is not only structurally important, but zinc signals can also act as a second messenger. This research investigates zinc signals in T cell activation and their function in T helper cell 1 differentiation. For this purpose, peripheral blood mononuclear cells were activated via the T cell receptor-CD3 complex, and via CD28 as a costimulatory signal. Fast and long-term changes in intracellular zinc and calcium were monitored by flow cytometry. Further, interferon (IFN)-γ was analyzed to investigate the differentiation into T helper 1 cells. We show that fast zinc fluxes are induced via CD3. Also, the intracellular zinc concentration dramatically increases 72 h after anti-CD3 and anti-CD28 stimulation, which goes along with the high release of IFN-γ. Interestingly, we found that zinc signals can function as a costimulatory signal for T helper cell 1 differentiation when T cells are activated only via CD3. These results demonstrate the importance of zinc signaling alongside calcium signaling in T cell differentiation.

Keywords: T helper cell 1; differentiation; signaling; zinc.

MeSH terms

  • CD28 Antigens* / agonists
  • CD28 Antigens* / metabolism
  • CD3 Complex / metabolism
  • Calcium / metabolism
  • Cell Differentiation* / drug effects
  • Humans
  • Interferon-gamma* / metabolism
  • Ionophores / pharmacology
  • Lymphocyte Activation* / drug effects
  • Lymphocyte Activation* / immunology
  • Pyridines* / chemistry
  • Pyridines* / pharmacology
  • Signal Transduction / drug effects
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Th1 Cells / drug effects
  • Th1 Cells / immunology
  • Th1 Cells / metabolism
  • Thiones* / chemistry
  • Thiones* / pharmacology
  • Zinc* / metabolism
  • Zinc* / pharmacology

Substances

  • Calcium
  • CD28 Antigens
  • CD3 Complex
  • Interferon-gamma
  • Ionophores
  • Zinc
  • pyrithione
  • Pyridines
  • Thiones

Grants and funding

This research received no external funding.