CD16-Expressing CD8αα ⁺ T Lymphocytes in the Intestinal Epithelium: Possible Precursors of FcγR ^- CD8αα ⁺ T Cells

T lymphocytes normally express their Ag receptors in association with the CD3 proteins, which include CD3ζ. In CD3ζη null mice thymic and peripheral T lymphocytes do not express the TCR/CD3 complex on their surface due to retention in the endoplasmic reticulum of the remaining polypeptide chains. However, intestinal intraepithelial lymphocytes (iIEL) of CD3ζη null mice do express surface TCR, because the FcεRIγ chain replaced the CD3ζ chain in the TCR/CD3 complex. Here we report that in a subset of CD8αα + iIEL the presence of the FcεRIγ chain could be accounted for by the surface expression of the FcγRIII(CD16) complex. Because in wild-type (wt) mice only CD16 + iIEL coexpressed FcεRIγ and CD3ζ, we concluded that the presence of FcεRIγ was dictated by its required participation of CD16 complex. CD8αα + iIEL bearing CD16 and B220 were also detected in the intestinal mucosa of RAG-2 null mice from 12 days after birth onward. Two independent experimental settings were used in an attempt to demonstrate that CD16 + iIEL matured into CD16 - T cells. First, in the RAG-2 null mice, iIEL responded to in vivo administration of an anti-CD3ε mAb by progression to a more mature stage of development, characterized by a loss of CD16 and B220. Secondly, a conversion to CD16 - iIEL occurred upon transfer of wt CD16 + iIEL into RAG-2 null mice. We conclude from these experiments that in both RAG-2 null and wt mice, a precursor/progeny relationship may exists between CD16 + B220 + CD8αα + and CD16 - B220 - CD8αα + iIEL.