The Effector Differentiation of TCRαβ+CD8αα+ Intraepithelial Lymphocytes Is Reciprocally Regulated by BCL6 and BLIMP1

CD8αα+TCRαβ+ intraepithelial lymphocytes (IELs) play crucial roles in maintaining intestinal homeostasis and host protection. However, the functional regulation of these cells remains unclear. Here, we have discovered and characterized two distinct developmental stages within intestinal CD8αα+ αβ IELs: a stem-like, defined by BCL6, TCF1 and CD160 expression, and an effector-like, with Granzyme B expression and Prdm1 transcription, by sorting and transcriptional sequencing BCL6+CD160+ CD8αα+ αβ IELs and BCL6-CD160- CD8αα+ αβ IELs. Comparing transcriptional profiles of total CD8αα+ αβ IELs from BCL6-deficient, BLIMP1-deficient and TCF1-deficient mice compared with that from their WT littermate control mice, we found a critical antagonistic function between BCL6/TCF1 and BLIMP1 in governing the fate decisions of CD8αα+ αβ IEL subsets.