Human T helper (Th) cell lineage commitment is not directly linked to the secretion of IFN‐γ or IL‐4: Characterization of Th cells isolated by FACS based on IFN‐γ and IL‐4 secretion

Abstract

Upon activation in vitro, only a fraction of the bulk human T helper cell cultures secret the hallmark Th1/2 cytokines (IFN‐γ for Th1 and IL‐4 for Th2, respectively). It is uncertain whether these IFN‐γ–/IL‐4– cells are differentiated Th1 or Th2 cells. Here, we have characterized live IFN‐γ+, IL‐4+ and IFN‐γ–/IL‐4– cells isolated from Th cell cultures treated under Th1 or Th2 polarizing conditions by employing affinity matrix capture technology. RNA samples from the sorted cells were analyzed by real time RT‐PCR and microarrays. The double negative cells from either Th1 or Th2 cultures expressed lower levels of Th1/Th2 marker cytokine genes (IFNγ, IL4, and IL5). However, they were comparable with the IFN‐γ+ or IL‐4+ cells in the expression levels of other Th1/Th2 marker genes (GATA3, Tbet, and IL12Rβ2). Most importantly, these double negative cells were already committed in their Th1/Th2 lineages. Gene expression profiling analysis showed that very few previously identified Th1/Th2 marker genes were differentially expressed between the IFN‐γ or IL‐4 producers and the non‐producers, further underscoring the similarity between these two groups.

The transcription factors T-bet and GATA-3 control alternative pathways of T-cell differentiation through a shared set of target genes

“…Only a proportion of human Th1 cells expressed IFN-␥ protein but almost all cells expressed T-bet, confirming the cells' Th1 phenotype (Fig. S1) and consistent with previous results (30). Th2 cells did not express T-bet but did express CRTh2 (Fig.…”

Effects of a Th1- versus a Th2-biased immune response in protection against Helicobacter pylori challenge in mice

“…However, since other cytokine responses that are sometimes thought of as Th1 biased (e.g. IL-2 and IL-12) showed a different pattern, the Th1 versus Th2 dichotomy is undoubtedly oversimplified, even in mice [29,30]. Mice immunized with LPS−/CT were not protected from challenge despite the presence of a diverse and robust H. pylori specific immune response.…”

Curcumin regulated shift from Th1 to Th2 in trinitrobenzene sulphonic acid-induced chronic colitis

“…The proportion of IFN-γ/IL-4 is reported as an important factor in regulating the shift of Th1/Th2 [19] . The relative abundance of mRNA in colon mucosa is a local index of Th1/Th2.…”