Cytokine/Antibody complexes: an emerging class of immunostimulants.
In recent years, complexes formed from a cytokine and antibodies against that respective cytokine (cytokine/Ab complex) have been shown to induce remarkable powerful changes in the immune system. Strong interest exists especially for complexes formed with Interleukin (IL)-2 and anti-IL-2-antibody (IL-2/Ab complex). IL-2/Ab complex activates maturation and proliferation in CD8(+) T cells and natural killer (NK) cells to a much higher degree than conventional IL-2 therapy. In addition, IL-2/Ab complex does not stimulate regulatory T cells as much as IL-2 alone. This suggests the possibility to replace the conventional IL-2 therapy with a therapy using low-dose IL-2/Ab complex. Further synthetic cytokine/Ab complexes are studied currently, including IL-3/Ab complex for its effects on the mast cell population, and IL-4/Ab complex and IL-7/Ab complex for inducing B and T cell expansion and maturation. Cytokine complexes can also be made from a cytokine and its soluble receptor. Pre-association of IL-15 with soluble IL-15 receptor alpha produces a complex with strong agonistic functions that lead to an expansion of CD8(+) T cells and NK cells. However, cytokine/Ab complexes also occur naturally in humans. A multitude of auto-antibodies to cytokines are found in human sera, and many of these auto-antibodies build cytokine/Ab complexes. This review presents naturally occurring auto-antibodies to cytokines and cytokine/Ab complexes in health and disease. It further summarizes recent research on synthetic cytokine/Ab complexes with a focus on the basic mechanisms behind the function of cytokine/Ab complexes.
Mostböck
Sven
S
Institute of Immunology, University of Regensburg, Franz-Josef-Strauss Allee 11, 93053 Regensburg, Germany. sven.mostboeck@klinik.uni-regensburg.de
D000276:Adjuvants, Immunologic / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000097:blood* / Q000276:immunology / Q000627:therapeutic use; D000936:Antigen-Antibody Complex / Q000097:blood* / Q000276:immunology; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D016207:Cytokines / Q000097:blood* / Q000276:immunology; D004194:Disease / Q000209:etiology; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D001323:Autoantibodies; D016207:Cytokines