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Showing papers by "Joshua D. Rabinowitz published in 1997"


Journal ArticleDOI
TL;DR: The calcium response of a peptide–major histocompatibility complex-specific CD4+ T lymphocyte line at the single cell level is characterized using a variety of ligands, alone and in combination, and the time between the first T cell–antigen-presenting cell contact and the onset of the calcium signal is measured.
Abstract: Summary We have characterized the calcium response of a peptide‐major histocompatibility complex (MHC)-specific CD4 1 T lymphocyte line at the single cell level using a variety of ligands, alone and in combination. We are able to distinguish four general patterns of intracellular calcium elevation, with only the most robust correlating with T cell proliferation. Whereas all three antagonist peptides tested reduce the calcium response to an agonist ligand, two give very different calcium release patterns and the third gives none at all, arguing that ( a ) antagonism does not require calcium release and ( b ) it involves interactions that are more T cell receptor proximal. We have also measured the time between the first T cell‐antigen-presenting cell contact and the onset of the calcium signal. The duration of this delay correlates with the strength of the stimulus, with stronger stimuli giving a more rapid response. The dose dependence of this delay suggests that the rate-limiting step in triggering the calcium response is not the clustering of peptide‐MHC complexes on the cell surface but more likely involves the accumulation of some intracellular molecule or complex with a half-life of a few minutes.

195 citations


Journal ArticleDOI
TL;DR: T cell recognition of two distinct complexes, one short-lived and the other long-lived, formed during the binding of an altered myelin basic protein peptide to I-Ak are described.
Abstract: Helper T cells are triggered by molecular complexes of antigenic peptides and class II proteins of the major histocompatibility complex . The formation of stable complexes between class II major histocompatibility complex proteins and antigenic peptides is often accompanied by the formation of a short-lived complex. In this report, we describe T cell recognition of two distinct complexes, one short-lived and the other long-lived, formed during the binding of an altered myelin basic protein peptide to I-Ak. One myelin basic protein-specific T cell clone is triggered by only the short-lived complex, and another is triggered by only the stable complex. Thus, a single peptide bound to a particular class II molecule can activate different T cells depending on the conditions of the binding reaction.

25 citations


Journal ArticleDOI
TL;DR: While IL-1β was moderately toxic and had no effect on recovery of peripheral blood counts after ABMT, the increased number of bone marrow CFU-GM suggests that the addition of G- or GM-CSF to a short course of IL- 1β may accelerate hematologic recovery.
Abstract: A phase I trial of recombinant human interleukin-1 β (OCT-43) following high-dose chemotherapy and autologous bone marrow transplantation

17 citations


Journal ArticleDOI
TL;DR: Screening for effects of cation channel blockers on the metabolism of a variety of human and murine cell lines revealed that low concentrations of clofilium but not other potassium channel blockers cause lymphoma apoptosis, demonstrating that effects of cl ofilium found in other studies may not be due to changes in plasma membrane potassium conductance.

17 citations