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

O Boyman, M Kovar, MP Rubinstein, CD Surh, J Sprent - Science, 2006 - science.org
O Boyman, M Kovar, MP Rubinstein, CD Surh, J Sprent
Science, 2006science.org
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 …
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.
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