The power of combinatorial immunology: IL-12 and IL-12-related dimeric cytokines in infectious diseases.
Appropriate induction of a Th1 immune response is required for effective antimicrobial immunity. However, dysregulated Th1 immune responses after infection may also lead to immunopathology. Thus, cell-mediated immune responses have to be tightly regulated. Upon infection, the production of interleukin (IL)-12, a heterodimeric cytokine composed of a p35 and a p40 subunit, is the dominant factor in Th1 cell development. The recent discovery of novel dimeric cytokines closely related to IL-12 add now to our understanding of cellular immunity and the fine tuning of T cell responses. At the onset of infection, IL-27, a heterodimer composed of the IL-12p40-related protein EBI-3 (Epstein-Barr virus-induced gene 3) and the IL-12p35-related protein p28 induces the expression of a functional IL-12 receptor in naive CD4+ T cells, making these cells sensitive to IL-12-mediated Th cell development. Later during infection, IL-23, a heterodimer composed of the IL-12p40 subunit and the IL-12p35-related molecule p19, preferentially acts on Th1 effector/memory CD4+ T cells. The IL-12p40 subunit can also form a homodimer, IL-12p80, which act as an IL-12 and IL-23 antagonist by competing at their receptors. This review focuses on these IL-12-related cytokines contributing to fine tuning of T cell responses after infection with intracellular pathogens.
Hölscher
Christoph
C
Junior Research Group Molecular Infection Biology, Research Center Borstel, Parkallee 22, 23845 Borstel, Germany. choelscher@fz-borstel.de
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D019281:Dimerization; D005786:Gene Expression Regulation; D006023:Glycoproteins / Q000737:chemistry / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D007239:Infections / Q000276:immunology*; D018664:Interleukin-12 / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D053765:Interleukin-12 Subunit p35; D053762:Interleukin-12 Subunit p40; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D015778:Minor Histocompatibility Antigens; D021122:Protein Subunits / Q000737:chemistry / Q000276:immunology; D018121:Receptors, Cytokine / Q000737:chemistry / Q000276:immunology; D018123:Receptors, Interleukin / Q000737:chemistry / Q000276:immunology*; D053707:Receptors, Interleukin-12; D018417:Th1 Cells / Q000276:immunology*
C097732:EBI3 protein, human; D006023:Glycoproteins; C508858:IL12A protein, human; C508840:IL23A protein, human; D053765:Interleukin-12 Subunit p35; D053762:Interleukin-12 Subunit p40; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins; C464565:MYDGF protein, human; D015778:Minor Histocompatibility Antigens; D021122:Protein Subunits; D018121:Receptors, Cytokine; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; D018664:Interleukin-12