Selective stimulation of T cell subsets with antibody-cytokine immune complexes.
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.
Boyman
Onur
O
Department of Immunology, IMM4, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Kovar
Marek
M
Rubinstein
Mark P
MP
Surh
Charles D
CD
Sprent
Jonathan
J
D019264:Adoptive Transfer; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000494:pharmacology; D000936:Antigen-Antibody Complex / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D049109:Cell Proliferation; D004797:Enzyme-Linked Immunosorbent Assay; D007156:Immunologic Memory; D007376:Interleukin-2 / Q000276:immunology* / Q000494:pharmacology; D015847:Interleukin-4 / Q000276:immunology; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D015375:Receptors, Interleukin-2 / Q000032:analysis / Q000276:immunology / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D015847:Interleukin-4