Reduced local immunity in HPV-related VIN: expression of chemokines and involvement of immunocompetent cells.
Usual type VIN is a premalignant disorder caused by persistent HPV infection. High prevalence of VIN in immuno-suppressed women suggests that a good innate and adaptive immune response is important for defense against HPV. Here, we explored expression levels of chemokines and related these to the presence or absence of immuno-competent cells (dendritic and T-cells) in affected (HPV-positive VIN) and non-affected (HPV-negative) vulvar tissues from the same patients. Combining microarray data with quantitative real-time RT-PCR, it was observed that several important chemokines were differentially expressed between VIN and control samples (up-regulation of IL8, CXCL10, CCL20 and CCL22 and down-regulation of CXCL12, CCL21 and CCL14). Furthermore, an increased number of mature dendritic cells (CD208+) seemed to be bottled up in the dermis, and although a T-cell response (increased CD4+ and CD8+ cells) was observed in VIN, a much larger response is required to clear the infection. In summary, it seems that most mature dendritic cells do not receive the proper chemokine signal for migration and will stay in the dermis, not able to present viral antigen to naive T-cells in the lymph node. Consequently the adaptive immune response diminishes, resulting in a persistent HPV infection with increased risk for neoplasia.
Santegoets
Lindy A M
LA
Department of Obstetrics and Gynaecology, Erasmus University Medical Center, Rotterdam, The Netherlands. l.santegoets@erasmusmc.nl
van Seters
Manon
M
Heijmans-Antonissen
Claudia
C
Kleinjan
Alex
A
van Beurden
Marc
M
Ewing
Patricia C
PC
Kühne
Liesbeth C M
LC
Beckmann
Ilse
I
Burger
Curt W
CW
Helmerhorst
Theo J M
TJ
Blok
Leen J
LJ
D000328:Adult; D052685:Alphapapillomavirus; D018925:Chemokines / Q000235:genetics / Q000378:metabolism*; D003713:Dendritic Cells / Q000276:immunology*; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016867:Immunocompromised Host; D007150:Immunohistochemistry; D046228:Microarray Analysis; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000150:complications* / Q000378:metabolism / Q000821:virology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D013601:T-Lymphocytes / Q000276:immunology*; D014412:Tumor Virus Infections / Q000150:complications* / Q000378:metabolism / Q000821:virology; D015854:Up-Regulation; D002583:Uterine Cervical Neoplasms / Q000276:immunology* / Q000821:virology; D002578:Uterine Cervical Dysplasia / Q000276:immunology* / Q000821:virology
D018925:Chemokines