Detection of regulatory T cell phenotypic markers and cytokines in patients with human papillomavirus infection

• Published in: Journal of medical virology 2019-02, Vol.91 (2), p.317-325
• Main Authors: Bonin, Camila M., Padovani, Cacilda T. J., da Costa, Izaías P., Ávila, Leandro S., Ferreira, Alda Maria T., Fernandes, Carlos Eurico S., dos Santos, Andrielli R., Tozetti, Inês Aparecida
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; CD25 antigen; CD4 antigen; Cervical cancer; Cervix Uteri - pathology; Cervix Uteri - virology; cytokine/chemokine; Cytokines; Cytokines - analysis; Female; Foxp3 protein; Growth factors; Health risks; Human papillomavirus; Humans; Immune response; Immune system; Immunohistochemistry; Immunomodulation; Immunoregulation; Infections; Interleukins; Lesions; Lymphocytes; Lymphocytes T; Markers; Middle Aged; Papillomaviridae - immunology; Papillomavirus Infections - pathology; Papillomavirus Infections - virology; Paraffin; Paraffins; Patients; regulatory T cell; Risk analysis; Risk factors; Stroma; T-Lymphocyte Subsets - chemistry; T-Lymphocyte Subsets - immunology; T-Lymphocytes, Regulatory - chemistry; T-Lymphocytes, Regulatory - immunology; Transforming growth factor; Uterus; Viral Load; Virology; Young Adult
• ISSN: 0146-6615; 1096-9071
• DOI: 10.1002/jmv.25312

Infection with human papillomavirus (HPV) is the main cause of cervical cancer. Viral persistence is considered the main risk factor for neoplastic progression and evidence suggests that regulatory T cells (Treg) play an important role in the failure of viral elimination. The aim of this study was to detect phenotypic markers of Treg and cytokines interleukin (IL)‐10 and transforming growth factor (TGF)‐β, in the cervical microenvironment of HPV‐infected patients. One hundred and one samples of uterine cervix embedded in paraffin were analyzed. We used immunohistochemistry to examine the coexpression of the CD25/FOXP3 and CD4/TGF‐β markers, and the expression of GITR and IL‐10 in cells present in the cervical stroma. We detected a microenvironment composed of high proportions of CD25+FOXP3+, CD4+TGFβ+, IL‐10+, and GITR+ cells in samples with high viral loads and severe lesions of HPV‐infected patients. The abundance of these markers, indicative of the presence of Treg cells and immunosuppressive cytokines, was significantly associated with severe lesions and elevated viral loads in the examined samples. These results suggest that Treg cells may be involved in maintaining a microenvironment favorable for viral persistence and neoplastic progression. Our findings support those of previous studies that suggested that these markers could be used to predict HPV persistence and neoplastic progression, and as potential targets for immune response modulation. High proportions of CD25+FOXP3+, CD4+TGF?+, IL‐10+, and GITR+ cells at the site of HPV infection. Presence of Treg cells and immunosuppressive cytokines in the severe cervical lesions. Association observed between high viral loads and coexpression of CD25/FOXP3 in severe lesions. Analyzing the Treg cells using immunohistochemistry help to understand the immunosuppressive tumor microenvironment.