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).