Maximum Immunobioactivity of Murine Small Intestinal Intraepithelial Lymphocytes Resides in a Subpopulation of CD43+ T Cells

Abstract

CD43 has been linked to many function-associated T cell activities. Using mAbs that recognize two different CD43 determinants, we show that, although mouse small intestinal intraepithelial lymphocytes (IELs) expressed the CD43 core molecule reactive with mAb R2/60, only about one-half of the total IELs—including some but not all of the TCRαβ and TCRγδ cells—expressed the CD43 S7− reactive determinant. CD43 S7+ IELs secreted more IL-2, IL-4, IL-10, IL-17, and IFN-γ following anti-CD3 stimulation, and were >4-fold more cytotoxic in fresh isolates and >16-fold more cytotoxic after anti-CD3 stimulation, than S7− IELs. S7+ but not S7− IELs from the ileum of IL-10−/− mice spontaneously produced IFN-γ. In vivo BrdU uptake by IELs in non-Ag-primed mice was greatest in the S7+ population, indicating that significantly more S7+ IELs than S7− IELs undergo cell expansion under normal homeostatic conditions. DNA microarray analyses showed that S7+ IELs expressed higher levels of genes associated with activated T cells, whereas S7− IELs expressed genes used in the regulation of NK cells. These findings define two functionally distinct populations of IELs based on CD43 expression independent of TCR class, and they identify a subset of IELs that may serve as a target to better control intestinal inflammation.