Intestinal intraepithelial lymphocytes are a distinct set of γδ T cells

Abstract

Lymphocytes are most reliably subdivided on the basis of their receptors for antigen at the cell surface. Three subtypes of lym-phocytes are well defined: B cells that bear surface immunoglobulin and make antibody, CD4⁺T cells with CD3 αβ(3 receptors specific for antigen associated with class II major histocompatibility com-plex molecules, and CD8⁺T cells with CD3 αβ( receptors specific for antigen associated with class I MHC molecules. These T cells are responsible for known forms of cell-mediated immunity. The discovery of a third rearranging T-cell specific gene called γ(refs1 and 2) has revealed the presence of a new class of T cells bearing a new receptor type, CD3 γδ (refs 3–7). To date, neither the function nor the specificity of cells bearing this receptor has been determined. Because γδ T cells are the main lymphocyte of epidermis^8–9, it was proposed that such cells could be important in surveillance of all epithelia¹⁰. We have isolated intraepithelial lymphocytes from murine small intestine^11–13, and shown that they predominantly or exclusively express CD3 γδ receptors. Unlike the epidermal lymphocytes, these cells also express CD8, and they use a different V_γ gene to form their receptor. This strongly suggests that γδ T cells home in a very specific manner to epithelia, where they presumably mediate their function.