Document 0143
 DOCN  M95B0143
 TI    Induction of the increased Fyn kinase activity in anergic T helper type
       1 clones requires calcium and protein synthesis and is sensitive to
       cyclosporin A.
 DT    9511
 AU    Gajewski TF; Fields P; Fitch FW; Department of Pathology, Ben May
       Institute, University of; Chicago, IL 60637, USA.
 SO    Eur J Immunol. 1995 Jul;25(7):1836-42. Unique Identifier : AIDSLINE
       MED/95347378
 AB    Several alterations in T cell receptor-associated signal transduction
       have been observed following induction of anergy of T helper type 1
       (Th1) clones, including a modified intracellular free calcium ([Ca2+]i)
       response and increased kinase activity associated with the protein
       tyrosine kinase p59fyn. In the current study, we demonstrate that,
       although the kinetics of acquisition of both of these signaling
       alterations correlated with the generation of anergy, a normal calcium
       response returned within 48 h after removal from the anergizing
       stimulus, whereas the increased p59fyn activity persisted and the cells
       remained hyporesponsive. Generation of both the anergic state and the
       increased p59fyn activity was prevented in the presence of calcium-free
       medium, cycloheximide (CHX), or cyclosporin A (CsA), and could be
       mimicked by the calcium ionophore ionomycin. In contrast, the altered
       calcium response was inhibited by stimulation in the presence of
       calcium-free medium or CsA, but not CHX. Thus, surprisingly, these data
       suggest that a chronic elevation of [Ca2+]i is proximal to and necessary
       for the increase in p59fyn-associated kinase activity observed in
       anergic Th1 clones. Increased p59fyn activity, but not the altered
       calcium response, correlates with maintenance of the anergic state.
 DE    Animal  Antigens, CD3/PHYSIOLOGY  Calcium/*PHYSIOLOGY  *Clonal Anergy
       Cycloheximide/PHARMACOLOGY  Cyclosporine/*PHARMACOLOGY  Enzyme Induction
       In Vitro  Lymphocyte Transformation  Mice  Mice, Inbred DBA
       Proteins/BIOSYNTHESIS  Proto-Oncogene Proteins/*BIOSYNTHESIS  Signal
       Transduction  Support, Non-U.S. Gov't  Support, U.S. Gov't, P.H.S.  Th1
       Cells/*PHYSIOLOGY  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
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