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Defective T cell development and function in the absence of Abelson kinases.

Publication ,  Journal Article
Gu, JJ; Zhang, N; He, Y-W; Koleske, AJ; Pendergast, AM
Published in: J Immunol
December 1, 2007

Thymocyte proliferation, survival, and differentiation are tightly controlled by signaling from the pre-TCR. In this study, we show for the first time that the Abelson (Abl) kinases regulate proximal signaling downstream of the pre-TCR. Conditional deletion of Abl kinases in thymocytes reveals a cell-autonomous role for these proteins in T cell development. The conditional knockout mice have reduced numbers of thymocytes, exhibit an increase in the percentage of the CD4(-)CD8(-) double-negative population, and are partially blocked in the transition to the CD4(+)CD8(+) double-positive stage. Moreover, the total number of T cells is greatly reduced in the Abl mutant mice, and the null T cells exhibit impaired TCR-induced signaling, proliferation, and cytokine production. Notably, Abl mutant mice are compromised in their ability to produce IFN-positive CD8 T cells and exhibit impaired CD8(+) T cell expansion in vivo upon Listeria monocytogenes infection. Furthermore, Ab production in response to T cell-dependent Ag is severely impaired in the Abl mutant mice. Together these findings reveal cell-autonomous roles for the Abl family kinases in both T cell development and mature T cell function, and show that loss of these kinases specifically in T cells results in compromised immunity.

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Published In

J Immunol

DOI

ISSN

0022-1767

Publication Date

December 1, 2007

Volume

179

Issue

11

Start / End Page

7334 / 7343

Location

United States

Related Subject Headings

  • Thymus Gland
  • T-Lymphocytes
  • Signal Transduction
  • Receptors, Antigen, T-Cell
  • Pyrimidines
  • Proto-Oncogene Proteins c-abl
  • Piperazines
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
 

Citation

APA
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ICMJE
MLA
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Gu, J. J., Zhang, N., He, Y.-W., Koleske, A. J., & Pendergast, A. M. (2007). Defective T cell development and function in the absence of Abelson kinases. J Immunol, 179(11), 7334–7343. https://doi.org/10.4049/jimmunol.179.11.7334
Gu, Jing Jin, Nu Zhang, You-Wen He, Anthony J. Koleske, and Ann Marie Pendergast. “Defective T cell development and function in the absence of Abelson kinases.J Immunol 179, no. 11 (December 1, 2007): 7334–43. https://doi.org/10.4049/jimmunol.179.11.7334.
Gu JJ, Zhang N, He Y-W, Koleske AJ, Pendergast AM. Defective T cell development and function in the absence of Abelson kinases. J Immunol. 2007 Dec 1;179(11):7334–43.
Gu, Jing Jin, et al. “Defective T cell development and function in the absence of Abelson kinases.J Immunol, vol. 179, no. 11, Dec. 2007, pp. 7334–43. Pubmed, doi:10.4049/jimmunol.179.11.7334.
Gu JJ, Zhang N, He Y-W, Koleske AJ, Pendergast AM. Defective T cell development and function in the absence of Abelson kinases. J Immunol. 2007 Dec 1;179(11):7334–7343.

Published In

J Immunol

DOI

ISSN

0022-1767

Publication Date

December 1, 2007

Volume

179

Issue

11

Start / End Page

7334 / 7343

Location

United States

Related Subject Headings

  • Thymus Gland
  • T-Lymphocytes
  • Signal Transduction
  • Receptors, Antigen, T-Cell
  • Pyrimidines
  • Proto-Oncogene Proteins c-abl
  • Piperazines
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice