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.

TLDR

The study examined how adding or neutralizing IL‑12 in lymphocyte bulk cultures affects the in vitro development of antigen‑specific T cell lines and clones. The authors manipulated IL‑12 levels in bulk lymphocyte cultures and assessed the resulting cytokine profiles of derived T cell lines and clones. IL‑12 skewed antigen‑specific T cell lines toward a Th1 phenotype by reducing IL‑4 and increasing IFN‑γ production, while neutralizing IL‑12 or removing CD16+ cells promoted IL‑4 secretion; anti‑IFN‑γ did not block IL‑12’s effect, indicating IL‑12 and CD16+ cells inhibit IL‑4‑producing cells and induce Th1 responses.

Abstract

The effects exerted on the in vitro development of antigen-specific T cell lines and T cell clones by addition or neutralization of interleukin 12 (IL-12) in lymphocyte bulk culture were examined. T cell lines specific for Dermatophagoides pteronyssinus group I (Der p I) derived in the presence of IL-12 exhibited reduced ability to produce IL-4 and increased ability to produce interferon gamma (IFN-gamma), and developed into Der p I-specific CD4+ T cell clones showing a T helper type 0 (Th0)- or Th1-, instead of Th2-, like cytokine profile. In contrast, purified protein derivative (PPD)-specific T cell lines derived in the presence of anti-IL-12 antibody exhibited an increased ability to produce IL-4 and developed into PPD-specific CD4+ T cell clones showing a Th0-, instead of Th1-, 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-gamma 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 Th1-like responses.