IL-10 and TGF-β, but Not IL-17A or IFN-γ, Potentiate the IL-15-Induced Proliferation of Human T Cells: Association with a Decrease in the Expression of β2m-Free HLA Class I Molecules Induced by IL-15

Int J Mol Sci. 2024 Aug 29;25(17):9376. doi: 10.3390/ijms25179376.

Abstract

IL-15 is a homeostatic cytokine for human T and NK cells. However, whether other cytokines influence the effect of IL-15 is not known. We studied the impact that IL-10, TGF-β, IL-17A, and IFN-γ have on the IL-15-induced proliferation of human T cells and the expression of HLA class I (HLA-I) molecules. Peripheral blood lymphocytes (PBLs) were labeled with CFSE and stimulated for 12 days with IL-15 in the absence or presence of the other cytokines. The proportion of proliferating T cells and the expression of cell surface HLA-I molecules were analyzed using flow cytometry. The IL-15-induced proliferation of T cells was paralleled by an increase in the expression of HC-10-reactive HLA-I molecules, namely on T cells that underwent ≥5-6 cycles of cell division. It is noteworthy that the IL-15-induced proliferation of T cells was potentiated by IL-10 and TGF-β but not by IL-17 or IFN-γ and was associated with a decrease in the expression of HC-10-reactive molecules. The cytokines IL-10 and TGF-β potentiate the proliferative capacity that IL-15 has on human T cells in vitro, an effect that is associated with a reduction in the amount of HC-10 reactive HLA class I molecules induced by IL-15.

Keywords: CD8+ T cells; HC-10; HLA class I molecules; W6/32; cytokines; open conformers; proliferation.

MeSH terms

  • Cell Proliferation* / drug effects
  • Cells, Cultured
  • Histocompatibility Antigens Class I* / metabolism
  • Humans
  • Interferon-gamma* / metabolism
  • Interferon-gamma* / pharmacology
  • Interleukin-10* / metabolism
  • Interleukin-15* / metabolism
  • Interleukin-15* / pharmacology
  • Interleukin-17* / metabolism
  • Interleukin-17* / pharmacology
  • Lymphocyte Activation / drug effects
  • T-Lymphocytes* / cytology
  • T-Lymphocytes* / drug effects
  • T-Lymphocytes* / immunology
  • T-Lymphocytes* / metabolism
  • Transforming Growth Factor beta* / metabolism
  • Transforming Growth Factor beta* / pharmacology

Substances

  • Interferon-gamma
  • Interleukin-17
  • Transforming Growth Factor beta
  • Interleukin-10
  • Interleukin-15
  • Histocompatibility Antigens Class I
  • IL17A protein, human
  • IL15 protein, human
  • IL10 protein, human