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.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Durst M, Gissmann L, Ikenberg H, Hausen HZ: A papillomavirus DNA from a cervical carcinoma and its prevalence in cancer biopsies from different geographic regions. Proc Natl Acad Sci USA 80:3812–3815, 1983
Fuchs PG, Girardi F, Pfister HM: Human papillomavirus DNA in normal, metaplastic, preneoplastic and neoplastic epithelia of the cervix uteri. Int J Cancer 41:41–45, 1988
Lizard G, Chignol MC, Chardonnet Y, Souchier C, Bordes M, Schmitt D, Revillard JP: Detection of human papillomavirus DNA in CaSki and HeLa cells by fluorescent in situ hybridization. Analysis by flow cytometry and confocal laser scanning microscopy. J Immunol Methods 157:31–38, 1993
Stoler MH, Rhodes CR, Whitbeck A, Wolinsky SM, Chow LT, Broker TR: Human papillomavirus type 16 and 18 gene expression in cervical neoplasia. Hum Pathol 23:117–128, 1992
Lorincz AT, Reid R, Jenson AB, Greenberg MD, Lancaster W, Kurman RJ: Human papillomavirus infection of the cervix: Relative risk association of 15 common anogenital types. Obstet Gynecol 79(3):328–337, 1992
Stone KM: Epidemiologic aspects of genital HPV infection. Clin Obstet Gynecol 32(1):112–116, 1989
Schneider A, Kirchhoff T, Meinhardt G, Gissmann L: Repeated evaluation of human papillomavirus 16 status in cervical swabs of young women with a history of normal papanicolaou smears. Obstet Gynecol 79:683–688, 1992
Parazzini F, Vecchia CL, Negri E, Fedele L, Franceschi S, Gallotta L: Risk factors for cervical intraepithelial neoplasia. Cancer 69:2276–2282, 1992
Kemp EA, Hakenewerth AM, Laurent SL, Gravitt PE, Stoerker J: Human papillomavirus prevalence in pregnancy. Obstet Gynecol 79(5):649–656, 1992
Reid R: Biology and colposcopic features of human papillomavirus-associated cervical disease. Obstet Gynecol Clin North Am 20(1):123–151, 1993
Aiba S, Rokugo M, Tagami H: Immunohistologic analysis of the phenomenon of spontaneous regression of numerous flat warts. Cancer 58(6):1246–1251, 1986
Cochran AJ: Histology and prognosis in malignant melanoma. J Pathol 97:459–468, 1969
Shimokawara I, Imamura M, Yamanka N, Ishii Y, Kikuchi K: Identification of lymphocyte subpopulations in human breast cancer tissue and its significance: An immunoperoxidase study with anti-human T- and B-cell sera. Cancer 49:1456–1462, 1982
Vayrynen M, Syrjarvi K, Castren O, Saarikoski S: Immunopheno-types of lymphocytes in prospectively followed up human papillomavirus lesions of the cervix. Genitourin Med 61:190–196, 1985
Syrjanen K, Vayrynen M, Castren O, Mantyjarvi R, Yliskoski M: The relation between the type of immunoreactive cells found in human papillomavirus (HPV) lesions of the uterine cervix and the subsequent behavior of these lesions. Arch Gynecol 234:189–196, 1984
Pillai MR, Balaram P, Padmanabhan TK, Nair MK: Monoclonal antibody defined phenotypes of peripheral blood lymphocytes in cancer of the uterine cervix. Am J Reprod Immunol 14:141–143, 1987
Mohanty KC, Scott CS, Limbert HJ, Master PS: Circulating B and T lymphocyte subpopulations in patients with genital warts. Br J Clin Pract 41(2):601–603, 1987
Fujihashi K, McGhee JR, Lue C, Beagley KW, Taga T, Hirano T, Kishimoto T, Mestecky J, Kiyono H: Human appendix B cells naturally express receptors for and respond to interleukin 6 with selective IgA1 and IgA2 synthesis. J Clin Invest 88:248–252, 1991
Castello G, Esposito G, Stellato G, Mora LD, Abate G, Germano A: Immunological abnormalities in patients with cervical carcinoma. Gynecol Oncol 25:61–64, 1986
Becker J, Behem J, Loning TH, Reichart P, Geerlings H: Quantitative analysis of immunocompetent cells in human normal oral and uterine cervical mucosa, oral papillomas and leukoplakias. Arch Oral Biol 30(3):257–264, 1985
Ghosh AK, Moore M: Tumour-infiltrating lymphocytes in cervical carcinoma. Eur J Cancer 28A:1910–1916, 1992
Ferguson A, Moore M, Fox H: Expression of MHC products and leucocyte differentiation antigens in gynaecological neoplasms: An immunohistological analysis of the tumour cells and infiltrating leucocytes. Br J Cancer 52:551–563, 1985
Ioannides CG, Rashed S, Fisk B, Fan D, Itoh K, Freedman RS: Lymphocytes infiltrating ovarian malignant ascites: Modulation of IL-2-induced proliferation by IL-4 and of selective increase in CD8+ T cells by TNF-α. Lymphokine Cytokine Res 10(4):307–315, 1991
Poppema S, Brocker EB, Leij LD: In situ analysis of the mononuclear cell infiltrate in primary malignant melanoma of the skin. Clin Exp Immunol 51:77–82, 1983
Svennevig JL, Lunde OC, Holter J, Bjorysvik D: Lymphoid infiltration and prognosis in colorectal carcinoma. Br J Cancer 23:169–178, 1985
Nakagomi H, Petersson M, Magnusson I, Juhlin C, Matsuda M, Mellstedt H, Taupin J-L, Vivier E, Anderson P, Kiessling R: Decreased expression of the signal-transducingζ chains in tumorinfiltrating T-cells and NK cells of patients with colorectal carcinoma. Cancer Res 53:5610–5612, 1993
Finke JH, Zea AH, Stanley J, Longo DL, Mizoguchi H, Tubbs RR, Wiltrout RH, O'Shea JJ, Kudoh S, Klein E, Bukowski RM, Ochoa AC: Loss of T-cell receptorζ chain and p561ck in T-cells infiltrating human renal cell carcinoma. Cancer Res 53:5613–5616, 1993
McGhee JR, Mestecky J, Dertzbaugh MT, Eldridge JH, Hirasawa M, Kiyono H: The mucosal immune system: From fundamental concepts to vaccine development. Vaccine 10(2):75–88, 1992
Herberman RB, Ortaldo JR: Natural killer cells: Their role in defense against disease. Science 214:24–30, 1981
McKenzie J, King A, Hare J, Fulford T, Wilson B, Stanley M: Immunocytochemical characterization of large granular lymphocytes in normal cervix and HPV associated disease. J Pathol 165:75–80, 1991
Lehtinen M, Leminen A, Kuoppala T, Tikkaninen M, Lehtinen T, Lehtovirta P, Punnonen R, Vesterinen E, Paavonen J: Pre- and postreatment serum antibody responses to HPV 16 E2 and HSV 2 ICP8 proteins in women with cervical carcinoma. J Med Virol 37:180–186, 1992
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Bell, M.C., Edwards, R.P., Partridge, E.E. et al. CD8+ T lymphocytes are recruited to neoplastic cervix. J Clin Immunol 15, 130–136 (1995). https://doi.org/10.1007/BF01543104
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01543104