Natural killer cell stimulatory factor (interleukin 12 [IL-12]) induces T helper type 1 (Th1)-specific immune responses and inhibits the development of IL-4-producing Th cells.

Abstract

SummaryThe effects exerted on the in vitro development of antigen-specific T cell lines and T cell clones by addition or neutralization of interleukin 12 (I1:12) in lymphocyte bulk culture were examined. T cell lines specific for Dermatophagoides pteronyssinus group I (Der p I) derived in the presence of I1:12 exhibited reduced ability to produce I1:4 and increased ability to produce interferon "/(IFN-3~), and developed into Der p I-specific CD4 § T cell clones showing a T helper type 0 (Th0)-or Thl-, instead of Th2-, like cytokine profile. In contrast, purified protein derivative (PPD)-specific T cell lines derived in the presence of anti-I1:12 antibody exhibited an increased ability to produce I1:4 and developed into PPD-specific CD4 + T cell clones showing a Th0-, instead of Thl-, like profile. The influence of IL-12 on the cytokine secretion profile of Der p I-specific T cell lines was not prevented by addition to lymphocyte bulk cultures of anti-IFN-y antibody, but could be at least partially inhibited by the removal from bulk cultures of CD16 + cells. Thus, IL-12 and CD16 + cells appear to have inhibitory effects on the development of IL-4-producing cells and to play an inductive role in promoting Thl-like responses.

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.…”

Opuntia humifusamodulates morphological changes characteristic of asthma via IL-4 and IL-13 in an asthma murine model

“…Th1-related cytokines include interferon gamma (IFN-γ), which affects the severity of asthma [4], and interleukin 12 (IL-12), which induces Th1 cells and suppresses Th2 cells [5,6]. Th2-related cytokines include IL-4, IL-5, IL-13, and Th17-related cytokines (tumor necrosis factor-alpha (TNF-α) IL-6, and IL-1β) [7].…”

Construction of a recombinant adeno-associated virus (rAAV) vector expressing murine interleukin-12 (IL-12)

“…4,6 IL-12 or IL-12 signaling pathways have also been shown to play a critical role in directing T helper 1 type differentiation, ultimately resulting in cell-mediated immunity. [7][8][9][10] The major sources of IL-12 include antigen-stimulated macrophages and B cells in peripheral blood mononuclear cells (reviewed in Ref. 11).…”