1. Главная
  2. Ресурсы
  3. Библиотечный поиск
Autonomous Maturationof α/β T LineageCells in the Absenceof Cooh-Terminal SrcKinase (Csk) Christian SchmedtAlexander Tarakhovsky2001 год

Autonomous Maturation of α/β T Lineage Cells in the Absence of Cooh-Terminal Src Kinase (Csk)
статья из журнала

Полный текстСтраница публикацииПубликация в OpenAlex
Аннотация: The deletion of COOH-terminal Src kinase (Csk), a negative regulator of Src family protein tyrosine kinases (PTKs), in immature thymocytes results in the development of α/β T lineage cells in T cell receptor (TCR) β-deficient or recombination activating gene (rag)-1–deficient mice. The function of Csk as a repressor of Lck and Fyn activity suggests activation of these PTKs is solely responsible for the phenotype observed in csk-deficient T lineage cells. We provide genetic evidence for this notion as α/β T cell development is blocked in lck−/−fyn−/− csk-deficient mice. It remains unclear whether activation of Lck and Fyn in the absence of Csk uncouples α/β T cell development entirely from engagement of surface-expressed receptors. We show that in mice expressing the α/β TCR on csk-deficient thymocytes, positive selection is biased towards the CD4 lineage and does not require the presence of major histocompatibility complex (MHC) class I and II. Furthermore, the introduction of an MHC class I–restricted transgenic TCR into a csk-deficient background results in the development of mainly CD4 T cells carrying the transgenic TCR both in selecting and nonselecting MHC background. Thus, TCR–MHC interactions have no impact on positive selection and commitment to the CD4 lineage in the absence of Csk. However, TCR-mediated negative selection of csk-deficient, TCR transgenic cells is normal. These data suggest a differential involvement of the Csk-mediated regulation of Src family PTKs in positive and negative selection of developing thymocytes.
Год издания: 2001
Авторы: Christian Schmedt, Alexander Tarakhovsky
Издательство: Rockefeller University Press
Источник: The Journal of Experimental Medicine
Ключевые слова: T-cell and B-cell Immunology, Immune Cell Function and Interaction, CAR-T cell therapy research
Другие ссылки: The Journal of Experimental Medicine (PDF)
The Journal of Experimental Medicine (HTML)
Europe PMC (PubMed Central) (PDF)
Europe PMC (PubMed Central) (HTML)
PubMed Central (HTML)
PubMed (HTML)