In vivo accumulation of T cells in response to IL-2/anti-IL-2 mAb complexes is dependent in part on the TNF family ligand 4-1BBL

Immunol Cell Biol. 2012 Aug;90(7):743-7. doi: 10.1038/icb.2011.83. Epub 2011 Sep 27.

Abstract

Immune complexes combining IL-2 with particular anti-IL-2 antibodies can be used to selectively expand regulatory T cells or memory T cells. Combining IL-2 with anti-IL-2 (Clone S4B6) greatly enhances the biological potency of IL-2 in vivo leading to selective expansion of CD8 memory T cells and NK cells compared with regulatory T cells. Here we show that in vivo administration of IL-2/anti-IL-2 mAb (IL-2/mAb) complexes induces 4-1BB expression on both adoptively transferred antigen-specific memory CD8 T cells as well as on endogenous memory phenotype cells. Remarkably, the accumulation of adoptively transferred memory CD8 T cells following in vivo IL-2/mAb-complex treatment was found to be dependent in part on the presence of 4-1BBL in the host. These effects were independent of IL-2-induced cell division, suggesting that 4-1BBL-induced survival signals contribute to IL-2/mAb-complex-induced T-cell accumulation in vivo.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-1BB Ligand / deficiency
  • 4-1BB Ligand / genetics
  • 4-1BB Ligand / immunology*
  • Adoptive Transfer
  • Animals
  • Antibodies, Monoclonal / pharmacology*
  • CD8-Positive T-Lymphocytes / drug effects*
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cell Survival / genetics
  • Cell Survival / immunology
  • Flow Cytometry
  • Immunologic Memory / immunology
  • Interleukin-2 / immunology
  • Interleukin-2 / pharmacology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Tumor Necrosis Factor Receptor Superfamily, Member 9 / immunology
  • Tumor Necrosis Factor Receptor Superfamily, Member 9 / metabolism

Substances

  • 4-1BB Ligand
  • Antibodies, Monoclonal
  • Interleukin-2
  • Tumor Necrosis Factor Receptor Superfamily, Member 9