CD8+ T lymphocytes are recruited to neoplastic cervix

Abstract

ToliicIV distinguish normal cervical lymphocyte populations from phenotypes recruited to the cervix in response to cervical neoplasia, lymphocytes were isolated from normal and neoplastic cervix. A portion of the cervical transformation zone was obtained from 19 patients with pathologically confirmed cervical intraepithelial neoplasia and from 20 patients with normal cervices undergoing hysterectomy for benign indications. Mononuclear cells were harvested from cervical tissue using a serial, multienzymatic digestion procedure and enriched by density gradient centrifugation. Isolated cell populations were stained with surface marker-specific monoclonal antibodies and analyzed by fluorescent activated cell sorter to determine the percentage of B cells, total T cells, CD4+ T cells, CD8+ T cells, and natural killer (NK) cells. The distribution of circulating peripheral blood lymphocyte phenotypes was similar for both patients with neoplasia and normal controls. A marked disparity in the proportions of NK cells and T cells was demonstrated among lymphocyte phenotypes infiltrating the cervix. The percentage of CD4+ T cells and NK cells was significantly depressed (P = 0.04, P = 0.03, respectively) in dysplastic tissue as compared to normal cervical tissue. In contrast, the proportion of CD8+ T cells was significantly increased in the dysplastic tissue (P = 0.0001). Analysis of immunocompetent cells in the circulation appears to have little correlation with immunocytes present in the dysplastic epithelium. The depression in the proportion of CD4+ T lymphocytes and NK cells at the cervical squamocolumnar junction reflects a local recruitment of CD8+ T cells to the site of neoplasia in the cervix.