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 populations are the Th1 and Th2 cells, which stem from a common naive T helper precursor (Thp). In this study, we begin to dissect the signaling pathways selectively used by Th1 or Th2 cells as they mature from a common 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 ligand 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 peptides. These data provide a direct and sequential assessment of a signaling pathway utilization in peripheral T cells as they differentiate to their final functional states.
Sloan-Lancaster
J
J
Cell Biology and Metabolism Branch, National Institute of Child Health and Development, Bethesda, MD 20892, USA.
Steinberg
T H
TH
Allen
P M
PM
D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000502:physiology; D002454:Cell Differentiation / Q000276:immunology; D016764:Cell Polarity / Q000276:immunology; D005260:Female; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D006454:Hemoglobins / Q000276:immunology; D016130:Immunophenotyping; D008024:Ligands; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*
D006454:Hemoglobins; D008024:Ligands; D010446:Peptide Fragments; D002118:Calcium