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Itk and Fyn make independent contributions to T cell activation.

Liao XC, Littman DR, Weiss A - J. Exp. Med. (1997)

Bottom Line: Itk is a member of the Btk/Tec/Itk family of nonreceptor protein tyrosine kinases (PTKs), and has been implicated in T cell antigen receptor (TCR) signal transduction.Lck and Fyn are the Src-family nonreceptor PTKs that are involved in TCR signaling.These data support the notion that Itk and Fyn both make independent contributions to TCR-induced T cell activation.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Immunology, Howard Hughes Medical Institute, University of California, San Francisco, California 94143, USA.

ABSTRACT
Itk is a member of the Btk/Tec/Itk family of nonreceptor protein tyrosine kinases (PTKs), and has been implicated in T cell antigen receptor (TCR) signal transduction. Lck and Fyn are the Src-family nonreceptor PTKs that are involved in TCR signaling. To address the question of how these members of different families of PTKs functionally contribute to T cell development and to T cell activation, mice deficient for both Itk and either Lck or Fyn were generated. The Itk/Lck doubly deficient mice exhibited a phenotype similar to that of Lck-deficient mice. The phenotype of the Itk/Fyn doubly deficient mice was similar to that of Itk deficient mice. However the Itk/Fyn doubly deficient mice exhibited a more severe defect in TCR-induced proliferation of thymocytes and peripheral T cells than did mice deficient in either kinase alone. These data support the notion that Itk and Fyn both make independent contributions to TCR-induced T cell activation.

Show MeSH
Itk/Fyn doubly deficient mice showed similar phenotypes as  Itk− mice in T cell development. Thymocytes from +, itk−/−, fyn−/−,  and itk−/−fyn−/− mice were stained with antibodies against CD4, CD8,  and various other cell surface molecules, and were analyzed with flow cytometry. Shown are profiles of the thymocyte subpopulations with the  percentage of total cells in each quadrant as indicated.
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Figure 1: Itk/Fyn doubly deficient mice showed similar phenotypes as Itk− mice in T cell development. Thymocytes from +, itk−/−, fyn−/−, and itk−/−fyn−/− mice were stained with antibodies against CD4, CD8, and various other cell surface molecules, and were analyzed with flow cytometry. Shown are profiles of the thymocyte subpopulations with the percentage of total cells in each quadrant as indicated.

Mentions: Maturation of thymocytes takes place in an ordered sequence of developmental events (13). Early immature thymocytes do not express either the CD4 or the CD8 coreceptors (DN). As a result of pre-TCR signaling events, the DN cells acquire expression of both CD4 and CD8 to become DP cells. Subsequently, expression of one of the coreceptors is extinguished, and the thymocytes become mature CD4+ and CD8+ single positive T cells. Mice lacking Fyn, an Src family nonreceptor PTK have normal numbers of thymocyte and T cell subpopulations as well as normal levels of surface expression of the TCR chains (Table 1 and Fig. 1), consistent with previous reports (9, 10). On the other hand, mice deficient in Itk have a partial block in T cell development (Table 1 and Fig. 1) in agreement with our previous studies (5). Itk-deficient mice have reduced numbers of mature lymph node T cells as well as a reduced ratio of CD4 to CD8 single positive cells in the thymus and the periphery.


Itk and Fyn make independent contributions to T cell activation.

Liao XC, Littman DR, Weiss A - J. Exp. Med. (1997)

Itk/Fyn doubly deficient mice showed similar phenotypes as  Itk− mice in T cell development. Thymocytes from +, itk−/−, fyn−/−,  and itk−/−fyn−/− mice were stained with antibodies against CD4, CD8,  and various other cell surface molecules, and were analyzed with flow cytometry. Shown are profiles of the thymocyte subpopulations with the  percentage of total cells in each quadrant as indicated.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2199174&req=5

Figure 1: Itk/Fyn doubly deficient mice showed similar phenotypes as Itk− mice in T cell development. Thymocytes from +, itk−/−, fyn−/−, and itk−/−fyn−/− mice were stained with antibodies against CD4, CD8, and various other cell surface molecules, and were analyzed with flow cytometry. Shown are profiles of the thymocyte subpopulations with the percentage of total cells in each quadrant as indicated.
Mentions: Maturation of thymocytes takes place in an ordered sequence of developmental events (13). Early immature thymocytes do not express either the CD4 or the CD8 coreceptors (DN). As a result of pre-TCR signaling events, the DN cells acquire expression of both CD4 and CD8 to become DP cells. Subsequently, expression of one of the coreceptors is extinguished, and the thymocytes become mature CD4+ and CD8+ single positive T cells. Mice lacking Fyn, an Src family nonreceptor PTK have normal numbers of thymocyte and T cell subpopulations as well as normal levels of surface expression of the TCR chains (Table 1 and Fig. 1), consistent with previous reports (9, 10). On the other hand, mice deficient in Itk have a partial block in T cell development (Table 1 and Fig. 1) in agreement with our previous studies (5). Itk-deficient mice have reduced numbers of mature lymph node T cells as well as a reduced ratio of CD4 to CD8 single positive cells in the thymus and the periphery.

Bottom Line: Itk is a member of the Btk/Tec/Itk family of nonreceptor protein tyrosine kinases (PTKs), and has been implicated in T cell antigen receptor (TCR) signal transduction.Lck and Fyn are the Src-family nonreceptor PTKs that are involved in TCR signaling.These data support the notion that Itk and Fyn both make independent contributions to TCR-induced T cell activation.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Immunology, Howard Hughes Medical Institute, University of California, San Francisco, California 94143, USA.

ABSTRACT
Itk is a member of the Btk/Tec/Itk family of nonreceptor protein tyrosine kinases (PTKs), and has been implicated in T cell antigen receptor (TCR) signal transduction. Lck and Fyn are the Src-family nonreceptor PTKs that are involved in TCR signaling. To address the question of how these members of different families of PTKs functionally contribute to T cell development and to T cell activation, mice deficient for both Itk and either Lck or Fyn were generated. The Itk/Lck doubly deficient mice exhibited a phenotype similar to that of Lck-deficient mice. The phenotype of the Itk/Fyn doubly deficient mice was similar to that of Itk deficient mice. However the Itk/Fyn doubly deficient mice exhibited a more severe defect in TCR-induced proliferation of thymocytes and peripheral T cells than did mice deficient in either kinase alone. These data support the notion that Itk and Fyn both make independent contributions to TCR-induced T cell activation.

Show MeSH