Intestinal Intraepithelial Lymphocytes Contain a CD3⁻ CD7⁺ Subset Expressing Natural Killer Markers and a Singular Pattern of Adhesion Molecules

Abstract

Intestinal intraepithelial lymphocytes (i-IEL) represent one of the largest, non-organized lymphoid population in the body. They are located outside the epithelial basement membrane among the mucosal epithelial cells. We, and previously other groups, have reported the presence of a CD7+CD3-IEL subset in the epithelium of human small intestine. This subset is drastically reduced in coeliac disease (CD) patients. In the present work we accomplish a better phenotypic characterization of this CD3-IEL subset and demonstrate the expression of typical natural killer (NK) cell markers. Most, if not all, CD3-CD7+ cells express NKPR1 (CD161)[98% +/- 2] and CD122[92% +/- 6]. In addition, a variable percentage express CD2[55% +/- 16], CD94[24% +/- 18], CD56[44% +/- 21] and CD16[12% +/- 4], however, no CD57 expression was observed. Moreover, these cells contain perforin granules[75% +/- 5], supporting a potential cytolytic ability. Regarding adhesion molecules, CD18 and CD44 expression is absent, which is consistent with a limited capacity of migration. Altogether, these data suggest the presence of intraepithelial NK cells in human intestinal epithelium, a compartment where cytotoxic effectors have not been clearly defined.