title: Balance of apoptotic and anti-apoptotic marker and perforin granule release in squamous intraepithelial lesions. HIV infection leads to a decrease in perforin degranulation.
abstract: Cell-mediated cytotoxicity plays an important role in the regulation to HPV-associated cervical intraepithelial neoplasia. HIV co-infection is related to poorer prognosis and more rapid clinical progression to cancer. We evaluated the presence of cervical inflammatory cells, apoptotic (Bax, Bcl-2, FasL, NOS2, perforin) markers and the degranulating expressing cell marker (CD107a) in low and high squamous intraepithelial lesions (LSIL and HSIL, respectively) from HIV-negative and -positive women. Higher percentage of cervical CD4(+), CD8(+) T cells and macrophage were observed in LSIL and HSIL groups when compared with control, especially in epithelium and basal layer of epithelium. However, progression from LSIL to HSIL did not change the frequency of inflammatory cells. HIV-infection lead to a reduction on cervical CD4(+) T cell infiltration and an increased CD8(+) T cell distribution in LSIL groups. A balance between pro- and anti-apoptotic protein expressions was verified. Bax-expressing cells were present in all groups and were rarely expressed in keratinocytes in the epithelium in LSIL and control groups, but notably decreased in HSIL group. However, its frequency was enhanced in the basal layer of the epithelium meanly in LSIL group. Bcl2-expressing cells in the epithelium and the stroma were enhanced in HSIL group when compared with LSIL group. HIV-infection did not interfere in both expressions NOS2 expression was located on keratinocytes in both LSIL and HSIL groups when compared with control group. There were few FasL cervical expressing cells in all groups. Indeed, perforin was identified in few cervical cells. However, CD107a, a surface marker for cellular degranulation was significantly higher in epithelium, basal layer of epithelium and stroma in LSIL and HSIL, respectively, when compared with control group. These results support that HIV infection may induce reduction on inflammatory cervical cell degranulation corroborating to carcinogenesis process. This is the first description on the role of HIV in downregulation of perforin degranulation in the cervical lesions and it might be related to carcinogenesis.
authors.affiliation: Laboratory of Immunology and Immunogenetic in Infectious Diseases at Evandro Chagas Clinical Research Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
authors.forename: Ana Teresa G
authors.initials: AT
authors.lastname: Fernandes
authors.forename: Natalia Pereira
authors.initials: NP
authors.lastname: da Rocha
authors.forename: Elyzabeth
authors.initials: E
authors.lastname: Avvad
authors.forename: Beatriz J
authors.initials: BJ
authors.lastname: Grinsztejn
authors.forename: Fabio
authors.initials: F
authors.lastname: Russomano
authors.forename: Aparecida
authors.initials: A
authors.lastname: Tristão
authors.forename: Marcel de Souza Borges
authors.initials: Mde S
authors.lastname: Quintana
authors.forename: Mauricio A
authors.initials: MA
authors.lastname: Perez
authors.forename: Fátima
authors.initials: F
authors.lastname: Conceição-Silva
authors.forename: Maria da Gloria
authors.initials: Mda G
authors.lastname: Bonecini-Almeida
mesh_terms: D000293:Adolescent; D000328:Adult; D017209:Apoptosis / Q000502:physiology; D014408:Biomarkers, Tumor / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D060085:Coinfection / Q000378:metabolism* / Q000473:pathology; D003594:Cytoplasmic Granules / Q000378:metabolism; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000150:complications / Q000378:metabolism / Q000473:pathology; D054353:Perforin / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000378:metabolism / Q000473:pathology / Q000821:virology*
chemical_list: D014408:Biomarkers, Tumor; D054353:Perforin
keywords: Apoptosis; CTL; Cytotoxic dysfunction; HIV-infection; SIL; Uterine cervix