Biological insights into TCRγδ+ and TCRαβ+ intraepithelial lymphocytes provided by serial analysis of gene expression (SAGE)

Intraepithelial lymphocytes (IELs) are abundant, evolutionarily conserved T cells, commonly enriched in T cell receptor (TCR) gamma delta 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 TCR gamma delta (+) and TCR alpha beta (+) 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 TCR alpha beta (+) IELs, whereas differences between resident TCR gamma delta (+) IELs and TCR alpha beta (+) IELs are less obvious.