Immunocompetent Cells in Uterine Cervical Lesions of Human Papillomavirus Origin

Abstract

To elucidate the local immunological reactions operative in the human papillomavirus (HPV)-induced lesions of the uterine cervix, a total of 150 cervical biopsies containing a dysplastic or a neoplastic change with (CO, 97 cases) or without (NCO, 53 cases) a coexistent HPV lesion (a flat, an inverted or a papillomatous condyloma) were subjected to ANAE (acid Α-naphthyl acetate esterase) staining of the immunocompetent cells; B and T lymphocytes, mononuclear phagocytes (MPS cells). In addition, HPV antigens were demonstrated by an indirect immunoperoxidase-PAP method. Age of the patients did not influence the proportions of B, T and MPS cells. Degree of epithelial atypia was inversely related to proportion of B cells in NCO but not in CO series, and directly related to proportions of T cells in CO series, the latter T cell increase being most probably ascribable to the appearance of suppressor T cells. Unlike in the different types of skin warts (caused by divergent HPV types), the type of the cervical condyloma did not affect the proportions of B, T and MPS cells, suggesting a common HPV type as a causative agent of the latter. MPS and T cells were more numerous in HPV-positive condylomas than in HPV-negative ones, supporting the concept that cell-mediated immune mechanisms recognize the surface antigens of the virus-transformed cells coded by the viral genome in the host cell nuclei (HPV+). The findings are discussed in terms of the immune mechanisms involved in rejection of HPV lesions in general, and those of the uterine cervix especially. The full significance of these mechanisms can only be understood when adequate follow-up data of the lesions are at hand.

Immunosuppressive cytokine Interleukin-10 (IL-10) is up-regulated in high-grade CIN but not associated with high-risk human papillomavirus (HPV) at baseline, outcomes of HR-HPV infections or incident CIN in the LAMS cohort

“…In the early 1980s, these studies were extended to cervical HPV lesions using newly introduced monoclonal antibodies to enumerate the cell subsets within these tissue-infiltrating lymphocytes (TIL) [29,30]. Different subsets of lymphocytes (B cells, T helper cells; T suppressor cells) were present in abundance among these TILs, located subjacent to but also within the HPV lesions, CIN and CC [29,30]. In addition, other types of immunocompetent cells, including Langerhans cells and natural killer cells were also detected among these infiltrates [31,32].…”

“…Like studies enumerating immunocompetent cells among TILs in the baseline biopsies [29][30][31][32][33][34], also the present study suffers from the failure to provide any longitudinal data from the biopsies taken at FU visits [23,27]. It is to be emphasized that like the traffic (recirculation) of immunocompetent cells in the cervix, also the production of immune regulatory cytokines (like IL-10) is a highly dynamic process [14,15], being balanced and counterbalanced by a multitude of local and systemic stimuli that are impossible to record in single biopsies without a longitudinal setting.…”

HPV DNA Positivity and Natural Killer Cell Activity in the Clinical Outcome of Mild Cervical Dysplasia: Integration between Virus and Immune System

“…Recently, several studies have shown that women with HIV infection have an increased risk of lower genital tract neoplasia [11][12][13][14], including cer vical, vaginal and vulvar intraepithelial neoplasia, with a prevalence from 22 to 70%. Both humoral and cellmediated immunity against the different types of HPV lesions has been disclosed [26], and, according to current understanding, the impairment of cell-mediated immuni ty seems to be the main factor predisposing to the devel opment and persistence of HPV infection and related cer vical dysplasia. An investigation of T lymphocyte subsets in women with manifested genital HPV infection showed a lower percentage of CD4+ cells (helper/inducer) and a higher percentage of CD8+ cells (cytotoxic/suppressor) compared with women with normal cervical cytologic evaluation [21].…”

Pathobiology of papillomavirus-related cervical diseases: prospects for immunodiagnosis

“…They have been observed to vary considerably in number and distribution in genital warts, prompting speculation that this variability may reflect differences in host response to HPV-related lesions (81). Cellular infiltrates in the vicinity of cervical HPVrelated precursor lesions contain both B and T cells, although there is no clear explanation as to the significance of their presence (11,120). General studies of humoral immunity to papillomaviruses point to three humoral responses, including antibodies to HPV-derived proteins, the infected cells themselves, and antigens not directly associated with warts.…”

“…Immunohistochemical location of these proteins has not been demonstrated convincingly, leaving unclear their precise distribution and conditions under which they are expressed. RNA transcripts corresponding to these proteins have been identified in both cancer precursors and invasive cancers, suggesting that their expression is not limited to cells undergoing viral replication (20,120). Thus, it is likely that these proteins are produced even under circumstances in which viral integration has silenced expression of the other proteins (111).…”