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

Upon activation in vitro, only a fraction of the bulk human T helper cell cultures secret the hallmark Th1/2 cytokines (IFN-gamma for Th1 and IL-4 for Th2, respectively). It is uncertain whether these IFN-gamma-/IL-4- cells are differentiated Th1 or Th2 cells. Here, we have characterized live IFN-gamma+, IL-4+ and IFN-gamma-/IL-4- cells isolated from Th cell cultures treated under Th1 or Th2 polarizing conditions by employing affinity matrix capture technology.

Genetic reprogramming of primary human T cells reveals functional plasticity in Th cell differentiation.

Activation of naive T cells through the TCR and cytokine signals directs their differentiation into effector or memory subsets with different cytokine profiles. Here, we tested the flexibility of human Th1 or Th2 differentiation by forced expression of transcription factors T-bet and GATA-3. Ectopic expression of T-bet and GATA-3 in freshly isolated human T(N) cells resulted in their differentiation to a Th1 and Th2 phenotype, respectively, in the absence of polarizing cytokines.

Activated, but not resting human Th2 cells, in contrast to Th1 and T regulatory cells, produce soluble ST2 and express low levels of ST2L at the cell surface.

The T1/ST2 gene encodes, as a result of differential splicing, a cell surface protein (transmembrane form of T1/ST2, ST2L) and a soluble, secreted, protein (ST2). Here, we show that transcripts for both ST2L and ST2 are present in activated human Th2 clones, but not in Th1 and T regulatory clones. This activation-dependent expression of ST2L/ST2 transcripts was also found in short-term in vitro differentiated, activated CD4(+) Th2 cells.