Selective stimulation of T cell subsets with antibody-cytokine immune complexes

Science. 2006 Mar 31;311(5769):1924-7. doi: 10.1126/science.1122927. Epub 2006 Feb 16.

Abstract

Interleukin-2 (IL-2), which is a growth factor for T lymphocytes, can also sometimes be inhibitory. Thus, the proliferation of CD8+ T cells in vivo is increased after the injection of a monoclonal antibody that is specific for IL-2 (IL-2 mAb), perhaps reflecting the removal of IL-2-dependent CD4+ T regulatory cells (T regs). Instead, we show here that IL-2 mAb augments the proliferation of CD8+ cells in mice simply by increasing the biological activity of preexisting IL-2 through the formation of immune complexes. When coupled with recombinant IL-2, some IL-2/IL-2 mAb complexes cause massive (>100-fold) expansion of CD8+ cells in vivo, whereas others selectively stimulate CD4+ T regs. Thus, different cytokine-antibody complexes can be used to selectively boost or inhibit the immune response.

Publication types

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

MeSH terms

  • Adoptive Transfer
  • Animals
  • Antibodies, Monoclonal / immunology*
  • Antibodies, Monoclonal / pharmacology
  • Antigen-Antibody Complex / immunology*
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Proliferation
  • Enzyme-Linked Immunosorbent Assay
  • Immunologic Memory
  • Interleukin-2 / immunology*
  • Interleukin-2 / pharmacology
  • Interleukin-4 / immunology
  • Lymphocyte Activation*
  • Lymphocyte Count
  • Mice
  • Mice, Inbred C57BL
  • Receptors, Interleukin-2 / analysis
  • Receptors, Interleukin-2 / immunology
  • Receptors, Interleukin-2 / metabolism
  • Recombinant Proteins / pharmacology
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocytes, Regulatory / immunology

Substances

  • Antibodies, Monoclonal
  • Antigen-Antibody Complex
  • Interleukin-2
  • Receptors, Interleukin-2
  • Recombinant Proteins
  • Interleukin-4