SELECTIVE LOSS OF THE CALCIUM-ION SIGNALING PATHWAY IN T-CELLS MATURING TOWARD A T-HELPER 2-PHENOTYPE

In the CD4(+) T cell lineage, two well-defined differentiated populati ons are the Th1 and Th2 cells, which stern from a common naive T helpe r precursor (Thp). In this study, we begin to dissect the signaling pa thways selectively used by Th1 or Th2 cells as they mature from a comm on naive precursor in vitro. We show that the maturing Th1 cells mount a vigorous and specific Ca2+ transient upon contact with immunogenic ligand, which is enhanced over that of the naive progenitor cells, As the cells differentiate toward a Th2 phenotype, they quickly lose the ability to engage this pathway, indicating a developmental segregation of intracellular signaling utilization, Moreover, altered peptide lig and stimulation of the Th1 line stimulates a similar Ca2+ transient as native ligand stimulation of the naive precursors, consistent with a quantitative difference in intracellular signaling by these two peptid es, These data provide a direct and sequential assessment of a signali ng pathway utilization in peripheral T cells as they differentiate to their final functional states.