Evaluation of Langerhans’ Cells in the Cervical Epithelium of Women with CIN
December 1, 1999 3 minutes read
Evaluation of Langerhans’ Cells in the Cervical Epithelium of Women with CIN
Abstract & commentary
Synopsis: In patients with HPV/CIN, there is a decrease in immune-competent cells in the epithelium.
Source: Connor JP, et al. Gynecol Oncol 1999;75: 130-135.
For some time it has been known that both human papillomavirus (HPV) infection and high-grade cervical intraephithelial neoplasia (CIN) are more common in patients who are immunosuppressed. Iatrogenic suppression in organ transplant patients as well as HIV-induced suppression in patients with AIDS are both known to be associated with markedly increased rates of CIN.
Several studies have attempted to identify the cause for the increased attack rate of HPV/CIN in immunosuppressed patients. Several prior studies have focused on the immunocompetent cells in the cervical squamous epithelium. By general agreement, the most important cell appears to be the Langerhans’ cell (LC). This cell appears to be a tissue macrophage which is responsible for recognizing foreign antigens and presenting them to the lymph nodes where an appropriate response can be developed. While some studies have shown a decrease in LC in patients with CIN, other studies have not found a decrease in this cell population.
Connor and colleagues used paired cervical biopsies in both normal patients and patients with CIN to determine the number of LCs in each specimen. In order to identify the LCs, the specimens were prepared using a method that identifies the S-100 antibody, which is thought to be the important protein in the cell-mediated immune system of the cervix. The samples were also prepared for identification of HPV using the hybrid capture technique.
Connor et al determined that immune-competent LCs were significantly reduced in cases of cervical dysplasia, and were also reduced in samples positive for HPV DNA. As an unexpected result, Connor et al found that in both control women and in those with HPV/CIN, S-100 proteins were markedly increased in women with an acute inflammatory process. They postulate that HPV/CIN might decrease the immune competence of the cervical squamous epithelium thus allowing malignant transformation to occur.
Comment by Kenneth L. Noller, MD
When I entered medical school almost 35 years ago, the whole topic of immunology was covered during one long lecture. The subdivisions of lymphocytes, the production of antibodies, and the results of alterations of the system were largely unknown. During the intervening years, it has become clear that many human diseases are due either to underexpression or overexpression of the immune response. Significant advances have been made in the understanding of the various components of both cell-mediated and humoral responses to outside stimuli, and perhaps most importantly, it has become clear that the development of malignancy may well "always" represent a malfunction or inadequacy of the immune response.
For more than a decade, it has been known that immunocompromised patients often develop cervical neoplasia than normal individuals. Yet only recently have techniques become available that can focus on specific elements of the immune response in the cervical epithelium. Connor et al have done an excellent job of demonstrating that cases of CIN are associated with a marked decrease in the tissue macrophages (Langerhans’cells) that are responsible for the cell-mediated antibody response of the cervical epithelium. They conclude that HPV (or CIN) causes a reduction in these immune-competent cells by an unknown mechanism. However, because there are not "before and after" samples, an equally plausible explanation would be that the patients had a decrease in immune competent cells to begin with, and, thus, were more susceptible to attack by HPV.
This information may be of more than academic interest to the practicing clinician in the future. We have known for a long time that recurrences of CIN are less frequent in patients who have developed infection following cold knife conization, or who have been treated by techniques that cause an intense tissue reaction. In the future, we may be treating cervical neoplasia medically by the application of topical medications that modify (enhance) tissue immune response. These so-called "immune response modulators" are just beginning to be studied in detail. While early studies suggest that these drugs may be used to treat numerous diseases, their specific effect on the cervical epithelium will need to await extensive study.
Which of the following cells is responsible for the cell-mediated immune response in the cervical epithelium?
a. Basal cell
b. Intermediate cell
c. Tissue macrophage
d. NK lymphocyte
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