Biological Insights into TCRγδ+ and TCRαβ+ Intraepithelial Lymphocytes Provided by Serial Analysis of Gene Expression (SAGE)

Abstract

Intraepithelial lymphocytes (IELs) are abundant, evolutionarily conserved T cells, commonly enriched in T cell receptor (TCR) gammadelta expression. However, their primary functional potential and constitutive activation state are incompletely understood. To address this, serial analysis of gene expression (SAGE) was applied to murine TCRgammadelta+ and TCRalphabeta+ intestinal IELs directly ex vivo, identifying 15,574 unique transcripts that collectively portray an "activated yet resting," Th1-skewed, cytolytic, and immunoregulatory phenotype applicable to multiple subsets of gut IELs. Expression of granzymes, Fas ligand, RANTES, prothymosin beta4, junB, RGS1, Btg1, and related molecules is high, whereas expression of conventional cytokines and high-affinity cytokine receptors is low. Differentially expressed genes readily identify heterogeneity among TCRalphabeta+ IELs, whereas differences between resident TCRgammadelta+ IELs and TCRalphabeta+ IELs are less obvious.

DifferentialLy49eExpression Pathways in Resting versus TCR-Activated Intraepithelial γδ T Cells

“…Because freshly isolated Ly49E low iIELs do not contain Ly49e Pro2 transcripts, suggesting Ly49e Pro3 promoter activity by analogy with Ly49E low -expressing in vitro TCRactivated DETCs, they probably represent cells that are TCR triggered in vivo. This would be consistent with the activated, yet resting phenotype that has been demonstrated for iIELs (35). Interestingly, Pro2 transcripts were also not present in freshly isolated, mature fetal thymic CD24 low CD122 + Ly49E low Vg3 T cells, the precursors of DETCs, suggesting that these thymocytes are TCR activated in vivo as well.…”

Cutting Edge: A Chemical Genetic System for the Analysis of Kinases Regulating T Cell Development

“…Indeed, whereas identification of cell lines or transgenic mice expressing a biologically relevant level of a transgene can be problematic, the capacity to use ASKAs to regulate kinase activity may allow one to use mice or cell lines grossly overexpressing a particular kinase. The relative ease of ASKA construction (successfully applied to v-Src, CDK2, Fus3, CAMKII␣ (4)), the specificity of the inhibitor's effects; the broad range of kinase activity achievable, and the closer correlation of biological outcome with kinase activity, as opposed to inducible levels of gene expression (26,27) suggest that ASKA technology should be usefully applied to many kinases emerging from the expression profiling of lymphoid cells (28,29) and from genome sequencing.…”

Recognition of Double-Stranded RNA by TLR3 Induces Severe Small Intestinal Injury in Mice

“…The CD8␣␤ ϩ IELs bear the hallmarks of adaptive immune cells. In contrast, the CD8␣␣ ϩ IELs possess many "unconventional" features that distinguish them from conventional CD8 ϩ T cells and are considered innate immune cells (3)(4)(5)(6)(7)(8).…”