Regulation of expression of SLAMF4 on the surface of mucosal lymphocytes

SLAMF4 is a cell surface receptor, which is primarily known as a regulator of cytotoxicity and cytokine secretion by mouse NK cells upon engagement with its counter-structure CD48. Here, we found SLAMF4 is highly expressed on the surface of most mucosal CD8+ T cells, whereas it is only expressed on some CD44+ CD8+ splenic cells. Upon transfer of naïve SLAMF4− CD8+ T cells derived from Thy1.2+ B6 mice into Thy1.2− B6, donor cells were found to express SLAMF4 after entry into the mucosa. The increase in SLAMF4+ CD8+ cells was due to upregulation of the receptor gene rather than to expansion of a small subset of memory CD8+ T cells. Consistent with the high level of IL-15 in the intestinal mucosa and its requirement for the maintenance of memory CD8+ T cells, we found that recombinant IL-15 induces SLAMF4, particularly the short isoform of SLAMF4, expression on CD8+ T cells. Costimulation with αSLAMF4 significantly increased the αCD3ϵ-induced infiltration of CD8+ T cells in small intestine and exacerbated the inflammation in the small intestine of IL-10-IRES-GFP reporter mouse. As control, αSLAMF4 alone did not cause inflammation in the intestine. In conclusion, the differential expression on mucosal CD8+ T cells as well as the dual nature of SLAMF4 function suggests that SLAMF4 might be involved in regulating the fine balance between the maintenance of tolerance and immune surveillance in the intestinal mucosa.