Interleukin-12 and the regulation of innate resistance and adaptive immunity

Key Points Interleukin-12 (IL-12) is a heterodimeric pro-inflammatory cytokine that regulates T-cell and natural killer-cell responses, induces the production of interferon-γ (IFN-γ), favours the differentiation of T helper 1 (T H 1) cells and is an important link between innate resistance and adaptive immunity. Although phagocytes were reported originally to be the main cell types that produce IL-12, subsets of dendritic cells (DCs) are the first producers of IL-12 in response to pathogens during infections. The differential production of IL-12 by DC subsets in response to various pathogens is dependent on differences in the regulation of expression of the gene encoding IL-12, patterns of Toll-like receptor (TLR) expression, and cross-regulation between the different subsets, involving cytokines such as IL-10 and type I IFN. Maturation of CD4 + and CD8 + T cells into type-1 cytokine-producing cells is differentially regulated, indicating the different relative roles of IL-12 and other factors in favouring maturation of the two cell types. Recently, it has become evident, however, that T H 1 responses might take place in the absence of IL-12 and that IL-12 might be only one of the members of a family of heterodimeric cytokines, also including IL-23 and IL-27, that are involved in the regulation of T H 1 responses. Interleukin-12 (IL-12) is a heterodimeric pro-inflammatory cytokine that induces the production of interferon-γ (IFN-γ), favours the differentiation of T helper 1 (T H 1) cells and forms a link between innate resistance and adaptive immunity. Dendritic cells (DCs) and phagocytes produce IL-12 in response to pathogens during infection. Production of IL-12 is dependent on differential mechanisms of regulation of expression of the genes encoding IL-12, patterns of Toll-like receptor (TLR) expression and cross-regulation between the different DC subsets, involving cytokines such as IL-10 and type I IFN. Recent data, however, argue against an absolute requirement for IL-12 for T H 1 responses. Our understanding of the relative roles of IL-12 and other factors in T H 1-type maturation of both CD4 + and CD8 + T cells is discussed here, including the participation in this process of IL-23 and IL-27, two recently discovered members of the new family of heterodimeric cytokines.