Deficiencies in myeloid antigen-presenting cells in women with cervical squamous intraepithelial lesions.
BACKGROUND
There is little information on the function of dendritic cells in women with human papillomavirus (HPV)-related cervical squamous intraepithelial lesions (SILs). In the current study the functions of dendritic cells in the development of T-cell immunity in women with cervical SILs were assessed.


METHODS
The percentage of myeloid dendritic cells (MDCs) and plasmacytoid dendritic cells (PDCs) in peripheral blood were enumerated of 44 patients with SIL (low-grade, 19; high-grade, 25), 19 patients with atypical squamous cells of undetermined significance (ASCUS), and 18 controls. The expression of costimulatory receptors was assessed and the ability of monocyte-derived dendritic cells (MDDC) to present HPV16-E6 and HPV16-E7 antigens to autologous T cells.


RESULTS
Patients with either low (L)-grade or high (H)-grade SIL had significantly lower median plasma levels of interferon-gamma than did the controls (P = .038 and .031, respectively). Compared with the controls, patients with ASCUS or LSILs had significantly lower median percentages of MDCs (P = .002 and P < .001, respectively), and significantly lower median percentages of MDDCs that expressed CD86 (P < .001 and P = .003, respectively) and major histocompatability complex class-II antigen human leukocyte antigen DR (HLA-DR) (P = .012 and P < .001, respectively). T cells of patients with ASCUS or LSILs proliferated less than those of the controls in response to HPV16-E7 (P = .002 and .046, respectively).


CONCLUSIONS
Low levels of peripheral blood MDCs and of MDDCs expressing CD86 and HLA-DR suggest that deficiencies in the ability of MDDC to present antigen to autologous T cells may lead to persistent infection with HPV and the development of cervical SILs in HPV-infected women.
Lee
Bang-Ning
BN
Department of Hematopathology, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. blee@mdanderson.org
Follen
Michele
M
Rodriquez
Graciela
G
Shen
De-Yu
DY
Malpica
Anais
A
Shearer
William T
WT
Reuben
James M
JM
D000328:Adult; D017951:Antigen Presentation; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D008875:Middle Aged; D018307:Neoplasms, Squamous Cell / Q000276:immunology* / Q000821:virology; D009856:Oncogene Proteins, Viral / Q000276:immunology; D027383:Papillomaviridae; D050725:Papillomavirus E7 Proteins / Q000276:immunology; D030361:Papillomavirus Infections; D012097:Repressor Proteins / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D002577:Uterine Cervical Diseases; D002583:Uterine Cervical Neoplasms / Q000276:immunology* / Q000821:virology; D002578:Uterine Cervical Dysplasia / Q000276:immunology* / Q000821:virology
C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins