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Selective Stimulation of T Cell Subsets with Antibody-Cytokine Immune Complexes
Onur Boyman,1
Marek Kovar,1
Mark P. Rubinstein,1
Charles D. Surh,1
Jonathan Sprent1,2*
Abstract:
Interleukin-2 (IL-2), which is a growth factor for T lymphocytes,can also sometimes be inhibitory. Thus, the proliferation ofCD8+ T cells in vivo is increased after the injection of a monoclonalantibody that is specific for IL-2 (IL-2 mAb), perhaps reflectingthe removal of IL-2–dependent CD4+ T regulatory cells(T regs). Instead, we show here that IL-2 mAb augments the proliferationof CD8+ cells in mice simply by increasing the biological activityof preexisting IL-2 through the formation of immune complexes.When coupled with recombinant IL-2, some IL-2/IL-2 mAb complexescause massive (>100-fold) expansion of CD8+ cells in vivo,whereas others selectively stimulate CD4+ T regs. Thus, differentcytokine-antibody complexes can be used to selectively boostor inhibit the immune response.
1 Department of Immunology, IMM4, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. 2 Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, NSW 2010, Australia.
* To whom correspondence should be addressed. E-mail: j.sprent{at}garvan.org.au
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