Development of T _H 1 CD4 ⁺ T Cells Through IL-12 Produced by Listeria -Induced Macrophages

Abstract

Development of the appropriate CD4+ T helper (TH) subset during an immune response is important for disease resolution. With the use of naïve, ovalbumin-specific alpha beta T cell receptor transgenic T cell, it was found that heat-killed Listeria monocytogenes induced TH1 development in vitro through macrophage production of interleukin-12 (IL-12). Moreover, inhibition of macrophage production of IL-12 may explain the ability of IL-10 to suppress TH1 development. Murine immune responses to L. monocytogenes in vivo are of the appropriate TH1 phenotype. Therefore, this regulatory pathway may have evolved to enable innate immune cells, through interactions with microbial pathogens, to direct development of specific immunity toward the appropriate TH phenotype.

The secretory IFN-γ response of single CD4 memory cells after activation on different antigen presenting cell types

“…In addition, DC express higher densities of costimulatory molecules that may also contribute to the differences seen. Finally, IL-12 facilitates IFN-γ expression in T cells [15,16]. DC, capable of producing IL-12, can provide such "costimulation", while B cells, which do not produce IL-12, cannot.…”

“…An antigen encounter can lead to the activation of specific T cells, however, the outcome of T cell activation is thought to depend critically on the APC type/subtype on which the antigen is presented [12][13][14]. For example, the production of IFN-γ by primed Th1 memory cells is regulated by the ability of APC to produce IL-12 [15,16]. One might therefore assume that a memory T cell capable of producing IFN-γ will secrete this cytokine only when it encounters an antigen on a dendritic cell (DC) or a macrophage, but not on a B cell.…”

Microparticles released by Listeria monocytogenes-infected macrophages are required for dendritic cell-elicited protective immunity

“…After being engulfed by macrophages, Lm survives by disrupting the phagosomal membrane by secreting virulence factors including listerilysin O, and then escaping into the cytoplasm. In response to Lm, macrophages produce a wide variety of pro-inflammatory cytokines, including TNF-a, IL-1, IL-6, IL-12, IL-23, etc., 2,37,38 which are involved in host defense against this pathogen; however, whether macrophages adapt other pathways involved in the protective immunity remains elusive. The expression of the above cytokines by macrophages is due to recognition of bacterial components or products through pathogen-associated molecule pattern receptors, whose signalings commonly result in the activation of NF-kB and MAPK.…”

Linkage analysis of the genetic determinants of T-cell IL-4 secretion, and identification of Flj20274 as a putative candidate gene

“…Thus, the generation of Th1 cells is critically driven by the presence of IL-12, 3 with additional contributions from IL-18. 4 In contrast, the key determinant of Th2 differentiation is the availability of IL-4.…”