Abstract
BackgroundShb, a ubiquitously expressed Src homology 2 domain-containing adaptor protein has previously been implicated in the signaling of various tyrosine kinase receptors including the TCR. Shb associates with SLP76, LAT and Vav, all important components in the signaling cascade governing T cell function and development. A Shb knockout mouse was recently generated and the aim of the current study was to address the importance of Shb deficiency on T cell development and function.ResultsShb knockout mice did not display any major changes in thymocyte development despite an aberrant TCR signaling pattern, including increased basal activation and reduced stimulation-induced phosphorylation. The loss of Shb expression did however affect peripheral CD4+ TH cells resulting in an increased proliferative response to TCR stimulation and an elevated IL-4 production of naïve TH cells. This suggests a TH2 skewing of the Shb knockout immune system, seemingly caused by an altered TCR signaling pattern.ConclusionOur results indicate that Shb appears to play an important modulating role on TCR signaling, thus regulating the peripheral CD4+ TH2 cell response.
Highlights
Shb, a ubiquitously expressed Src homology 2 domain-containing adaptor protein has previously been implicated in the signaling of various tyrosine kinase receptors including the T cell receptor (TCR)
Effect of Shb null allele on blood cell numbers Since Shb has been demonstrated to interact with the TCR, and with other receptors that are important for the development and function of the hematopoietic system it was of interest to determine whether the loss of Shb expression would result in any alterations in the number of blood cells
Aberrant signal transduction in Shb knockout thymocytes TCR signaling is of uttermost importance in thymocyte development as many of the survival and death signals are mediated through the receptor
Summary
A ubiquitously expressed Src homology 2 domain-containing adaptor protein has previously been implicated in the signaling of various tyrosine kinase receptors including the TCR. Shb associates with SLP76, LAT and Vav, all important components in the signaling cascade governing T cell function and development. The primary aim of T cell development is to create a fully competent T lymphocyte population in the periphery, capable of quickly identifying pathogens yet nonresponsive to self-tissue [1,2]. To maintain this delicate balance, the immature thymocytes are subjected to rigorous control, where signaling through the T cell receptor (TCR) is of utmost importance [3,4,5]. Loss of early signaling elements, such as LAT or SLP76 has profound effects on T cell development and function, with an almost complete block at the very first thymocyte development step requiring TCR signaling, the b- selection, and with severely impaired peripheral responses as a consequence [11,19,20,21]
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