IL-15 induces type 1 and type 2 CD4+ and CD8+ T cells proliferation but is unable to drive cytokine production in the absence of TCR activation or IL-12 / IL-4 stimulation in vitro

Eur J Immunol. 2002 Feb;32(2):341-7. doi: 10.1002/1521-4141(200202)32:2<341::AID-IMMU341>3.0.CO;2-X.


Interleukin 15 (IL-15) is a pleiotropic cytokine produced principally by monocytes and affects both innate and acquired immunity. It has been shown that IL-15 is essential for the proliferation and maintenance of CD8+ memory cells but has little or no effect on naive CD8+ cells or CD4+ T cells. We report here, using an in vitro culture system of antigen-specific OVA TCR transgenic T cells as well as normal mouse T cell activated with anti-CD3 antibody that IL-15, at high concentrations, induced proliferation of both naive and memory CD4+ and CD8+ cells. IL-15 also enhanced the differentiation of type 1 (IFN-gamma-producing) and type 2 (IL-5-producing) CD4+ and CD8+ T cells under IL-12 and IL-4 driving conditions, respectively. However, IL-15 alone was not efficient in stimulating cytokine production of these cells in the absence of T cell subset driving cytokines (IL-12 or IL-4) and / or simultaneous TCR activation. Together, these results demonstrate that IL-15, at high dose, is a pan-T cell growth factor. The apparent requirement of IL-15 for the maintenance of memory CD8+ cell in vivo may reflect the exceptionally restricted nature of this subpopulation of cells for IL-15. The inability of IL-15 alone to stimulate cytokine synthesis also suggests that IL-15 on its own does not drive antigen-specific T cells to exhaustion. The levels of these cells are maintained by IL-15 and they are only mobilized to carry out effector functions when subsequently confronted with specific pathogens.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Differentiation / drug effects
  • Cell Division
  • Cytokines / biosynthesis*
  • Female
  • Immunologic Memory
  • In Vitro Techniques
  • Interleukin-12 / pharmacology
  • Interleukin-15 / pharmacology*
  • Interleukin-4 / pharmacology
  • Lymphocyte Activation / drug effects
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Ovalbumin / immunology
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Receptors, Antigen, T-Cell, alpha-beta / metabolism
  • Th1 Cells / cytology
  • Th1 Cells / drug effects
  • Th1 Cells / immunology
  • Th2 Cells / cytology
  • Th2 Cells / drug effects
  • Th2 Cells / immunology


  • Cytokines
  • Interleukin-15
  • Receptors, Antigen, T-Cell, alpha-beta
  • Interleukin-12
  • Interleukin-4
  • Ovalbumin