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1996-02-26
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Document 0535
DOCN M9620535
TI Early activation signal transduction pathways of Th1 and Th2 cell clones
stimulated with anti-CD3. Roles of protein tyrosine kinases in the
signal for IL-2 and IL-4 production.
DT 9602
AU Tamura T; Nakano H; Nagase H; Morokata T; Igarashi O; Oshimi Y; Miyazaki
S; Nariuchi H; Department of Allergology, University of Tokyo, Japan.
SO J Immunol. 1995 Nov 15;155(10):4692-701. Unique Identifier : AIDSLINE
MED/96062285
AB In the present experiments, TCR-CD3-associated early activation signal
transduction pathways were examined in Th1 and Th2 clones by the
stimulation with soluble monovalent anti-CD3 which resulted in efficient
production of IL-2 and IL-4 in Th1 and Th2 cells, respectively. Although
protein tyrosine kinases such as Fyn and ZAP-70 were activated in Th1
clones shortly after stimulation, these kinases in Th2 clones were not
activated; but, their activity in resting conditions was shown to be
decreased by the stimulation. In accordance with these findings, neither
phospholipase C-gamma 1 activation nor phosphatidyl
inositol-4,5-bisphosphate breakdown was induced in Th2 clones, in
contrast to positive responses in Th1 clones. The oscillation of
intracellular free Ca2+ concentration ([Ca2+]i) was a common signal for
the activation of both Th1 and Th2 clones; however, the [Ca2+]i
elevation in Th1 clones was herbimycin A sensitive, whereas that in Th2
was clone resistant, suggesting that the mechanism of the [Ca2+]i
elevation in Th2 cells is different from that in Th1 cells in terms of
the participation of protein tyrosine kinases. The anti-CD3 stimulation
did not cause Lck activation in either the Th1 or Th2 clone, although
remarkable activation was induced in both clones following anti-CD4
stimulation, indicating that Lck activation was not required for either
IL-2 or IL-4 production of Th cells. Taken together, these results
indicate that Th1 and Th2 cells are different from each other in early
activation signal transduction pathways, especially in the role of
protein tyrosine kinases.
DE Animal Antigens, CD3/*METABOLISM Clone Cells Enzyme Activation
Interleukin-2/*BIOSYNTHESIS Interleukin-4/*BIOSYNTHESIS Mice Mice,
Inbred C3H Mice, Inbred C57BL Protein-Tyrosine Kinase/*METABOLISM
Proto-Oncogene Proteins/*METABOLISM *Signal Transduction Support,
Non-U.S. Gov't Th1 Cells/*METABOLISM Th2 Cells/*METABOLISM JOURNAL
ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).