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Ex Vivo Infection of Human Lymphoid Tissue and Female Genital Mucosa with Human Immunodeficiency Virus 1 and Histoculture
Published on: October 12, 2018
HIV+ patients have increased lymphocyte infiltrates in CIN lesions
M C Bell1, D Schmidt-Grimminger, E Turbat-Herrera
1Department of Obstetrics and Gynecology, Louisiana State University, Shreveport, Louisiana 71130, USA.
Insights
Human immunodeficiency virus (HIV) infection in patients with cervical intraepithelial neoplasia (CIN) leads to increased lymphocytes and CD8+ T cells at the lesion site, potentially explaining more aggressive disease progression.
Area of Science:
- Immunology
- Oncology
- Virology
Background:
- Cervical intraepithelial neoplasia (CIN) can exhibit aggressive behavior in patients with human immunodeficiency virus (HIV).
- Understanding the immune microenvironment in CIN lesions is crucial for explaining disease progression in HIV-infected individuals.
Purpose of the Study:
- To investigate immunocyte infiltrates in CIN lesions from HIV-positive patients.
- To determine if local immunosuppression, indicated by reduced T cell infiltrates, contributes to the aggressive nature of CIN in HIV-infected individuals.
Main Methods:
- Cervical tissues from HIV-positive CIN patients, HIV-negative CIN patients, and normal controls were analyzed.
- Immunocyte markers including CD20 (B cells), CD4 (T helper cells), and CD8 (T suppressor/cytotoxic cells) were quantified.
- Image analysis software was used to assess cell surface markers in tissue sections.
Main Results:
- HIV-positive CIN tissues showed significantly higher numbers of B and T lymphocytes compared to HIV-negative CIN or normal tissues.
- A significant increase in CD8+ T cells was observed in HIV-positive CIN tissues.
- A trend towards a decreased CD4+/CD8+ ratio was noted in HIV-positive CIN patients, though not statistically significant.
Conclusions:
- HIV-positive cervical intraepithelial neoplasia (CIN) lesions recruit a greater number of lymphocytes to the neoplastic site.
- HIV infection may lead to a decreased CD4/CD8 ratio in infiltrating immunocytes within CIN lesions.
- Local immunomodulatory effects of HIV could be detectable early, potentially explaining the aggressive nature of CIN in HIV-positive individuals.
Objective:
The objective of our study was to analyze immunocyte infiltrates in CIN lesions from HIV+ patients to assess whether local immunosuppression, defined as a decrease in T cell infiltrates, could explain the aggressive nature of CIN in HIV-infected patients.
Materials And Methods:
Cervical tissue was obtained from 6 HIV+ CIN patients, 6 HIV- CIN patients, who underwent LLETZ (large loop excision of the transformation zone) for CIN, and 17 normal patients who underwent hysterectomy for benign indications. The following cell surface markers were analyzed: CD20 (B cells), CD4 (T helper cells), and CD8 (T suppressor/cytotoxic cells). Each tissue section was visualized with a Leica microscope at 400x and the image was captured for analysis by Harmony Group image analysis software.
Results:
A significantly higher number of lymphocytes (both B and T cells) was detected in the stroma of HIV+/CIN tissue compared to either HIV-/CIN or normal tissue. There was also a significant increase in CD8+ cells in the HIV+/CIN group compared to HIV-/CIN or normal tissue. There was a trend toward a decreased CD4+/CD8+ ratio in the HIV+/CIN compared to the other two groups; however, this did not reach statistical significance.
Conclusions:
This study indicates that HIV+/CIN cervical tissue has a greater number of tissue lymphocytes recruited to the neoplastic site compared to HIV- individuals. In addition, HIV+ patients may have a decreased CD4/CD8 ratio in locally infiltrating immunocytes in CIN lesions. The local immunomodulatory effects of HIV may be detectable early in infection and therefore may explain the aggressive nature of CIN in the HIV+ patient.
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