The purposes of this study were to examine the biologic effects of the engagement of the interleukin-7 receptor (IL-7R) with recombinant human interleukin-7 (rhIL-7) in immunophenotypically distinct T-lineage acute lymphoblastic leukemia (ALL) blasts and to elucidate the biochemical nature of the IL-7R-linked transmembrane signal in rhIL-7-responsive T-lineage ALL blast populations. In the abse...

Interleukin-7 receptor (IL-7R) levels are tightly controlled during ontogeny: high on double-negative (DN) cells, absent on double-positive (DP) cells, and high once again on thymocytes undergoing positive selection. To determine if loss of IL-7-mediated survival signals in DP cells is necessary for normal antigen-specific selection, we created T-lineage-specific IL-7R alpha chain (IL-7Ralpha) ...

Signals from the IL-7R are uniquely required for T cell development and maintenance, despite the resemblance of IL-7R to other cytokine receptors and the apparent sharing of common signaling pathways. This unique requirement could either reflect unique expression of IL-7R or IL-7, or it could indicate that the IL-7R delivers unique signals. To determine whether the IL-7R provided unique signals...

Allelic exclusion prevents pre-B cells from generating more than one functional H chain, thereby ensuring the formation of a unique pre-BCR. The signaling processes underlying allelic exclusion are not clearly understood. IL-7R-dependent signals have been clearly shown to regulate the accessibility of the Ig H chain locus. More recent work has suggested that pre-BCR-dependent attenuation of IL-...

Variable sensitivity to T-cell-receptor (TCR)- and IL-7-receptor (IL-7R)-mediated homeostatic signals among naïve T cells has thus far been largely attributed to differences in TCR specificity. We show here that even when withdrawn from self-peptide-induced TCR stimulation, CD8(+) T cells exhibit heterogeneous responses to interleukin-7 (IL-7) that are mechanistically associated with IL-7R expr...

The two tyrosine kinase receptors, c-kit and flt3, and their respective ligands KL and FL, have been demonstrated to play key and nonredundant roles in regulating the earliest events in hematopoiesis. However, their precise roles and potential interactions in promoting early lymphoid commitment and development remain unclear. Here we show that most if not all murine Lin(-/lo)Sca1(+)c-kit(+) bon...

CD1d-restricted Valpha24-invariant natural killer T cells (iNKTs) are important in immunoregulation. CD4(+) and CD4(-) iNKTs develop with similar frequencies in murine thymus and depend on interleukin-15 (IL-15) in periphery. However, homeostatic requirements of iNKTs have not been analyzed in humans. We evaluated thymic production, peripheral dynamics, and functional maturation of human iNKTs....