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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
Lack of a proliferative response with Itk−Fyn− splenocytes in  a MLR. Splenocytes from mice of the indicated genotypes were stimulated in vitro with irradiated splenocytes from C57BL/6 mice (broken  line), or from BALB/c mice (solid lines) for 96 h. Cell proliferation was  measured by [3H]thymidine incorporation after an additional 16 h. The  genotypes of mice are as indicated. Standard deviations for triplicate samples are shown as error bars along the y axis.
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Figure 3: Lack of a proliferative response with Itk−Fyn− splenocytes in a MLR. Splenocytes from mice of the indicated genotypes were stimulated in vitro with irradiated splenocytes from C57BL/6 mice (broken line), or from BALB/c mice (solid lines) for 96 h. Cell proliferation was measured by [3H]thymidine incorporation after an additional 16 h. The genotypes of mice are as indicated. Standard deviations for triplicate samples are shown as error bars along the y axis.

Mentions: To examine the impact of these kinases on antigen-dependent responses, mature T cells from mutant mice were also examined in MLR. Consistent with the results with anti-CD3 induced proliferation, Itk−Fyn− splenocytes responded very poorly to allogeneic MHC stimulation, whereas Itk-deficient splenocytes had an intermediate level of proliferation (Fig. 3). On the other hand, splenocytes lacking Fyn exhibited near normal alloantigen-induced proliferation (data not shown), consistent with previous studies (9, 10). These results support the notion that both Itk and Fyn functionally contribute to T cell responses to alloantigens.


Itk and Fyn make independent contributions to T cell activation.

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

Lack of a proliferative response with Itk−Fyn− splenocytes in  a MLR. Splenocytes from mice of the indicated genotypes were stimulated in vitro with irradiated splenocytes from C57BL/6 mice (broken  line), or from BALB/c mice (solid lines) for 96 h. Cell proliferation was  measured by [3H]thymidine incorporation after an additional 16 h. The  genotypes of mice are as indicated. Standard deviations for triplicate samples are shown as error bars along the y axis.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 3: Lack of a proliferative response with Itk−Fyn− splenocytes in a MLR. Splenocytes from mice of the indicated genotypes were stimulated in vitro with irradiated splenocytes from C57BL/6 mice (broken line), or from BALB/c mice (solid lines) for 96 h. Cell proliferation was measured by [3H]thymidine incorporation after an additional 16 h. The genotypes of mice are as indicated. Standard deviations for triplicate samples are shown as error bars along the y axis.
Mentions: To examine the impact of these kinases on antigen-dependent responses, mature T cells from mutant mice were also examined in MLR. Consistent with the results with anti-CD3 induced proliferation, Itk−Fyn− splenocytes responded very poorly to allogeneic MHC stimulation, whereas Itk-deficient splenocytes had an intermediate level of proliferation (Fig. 3). On the other hand, splenocytes lacking Fyn exhibited near normal alloantigen-induced proliferation (data not shown), consistent with previous studies (9, 10). These results support the notion that both Itk and Fyn functionally contribute to T cell responses to alloantigens.

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