Selective Stimulation of T Cell Subsets with Antibody-Cytokine Immune Complexes
Top Cited Papers
- 31 March 2006
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 311 (5769) , 1924-1927
- https://doi.org/10.1126/science.1122927
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.Keywords
This publication has 18 references indexed in Scilit:
- Tolerance, not immunity, crucially depends on IL-2Nature Reviews Immunology, 2004
- Cytokine control of memory T-cell development and survivalNature Reviews Immunology, 2003
- T Cell MemoryAnnual Review of Immunology, 2002
- Control of Homeostasis of CD8 + Memory T Cells by Opposing CytokinesScience, 2000
- Cytokine-binding proteins: stimulating antagonistsImmunology Today, 1995
- Heterodimerization of the IL-2 receptor β- and γ-chain cytoplasmic domains is required for signallingNature, 1994
- Enhancement of anti-tumor activity of recombinant interleukin-2 (rIL-2) by immunocomplexing with a monoclonal antibody against rIL-2Biotherapy, 1993
- Cloning of the γ Chain of the Human IL-2 ReceptorScience, 1992
- THE MULTI-SUBUNIT INTERLEUKIN-2 RECEPTORAnnual Review of Biochemistry, 1989
- Interleukin-2: Inception, Impact, and ImplicationsScience, 1988