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Clin Immunol. 2015 Dec;161(2):197-208. doi: 10.1016/j.clim.2015.09.003. Epub 2015 Sep 8.

Langerhans cells from women with cervical precancerous lesions become functionally responsive against human papillomavirus after activation with stabilized Poly-I:C.

Author information

1
Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA; Department of Obstetrics & Gynecology, University of Southern California, Los Angeles, CA, USA. Electronic address: Diane.DaSilva@med.usc.edu.
2
Department of Molecular Microbiology & Immunology, University of Southern California, Los Angeles, CA, USA.
3
Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA.
4
Groningen International Program of Science in Medicine, University of Groningen, Groningen, The Netherlands.
5
Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA; Department of Obstetrics & Gynecology, University of Southern California, Los Angeles, CA, USA.
6
Akela Pharma Inc., Austin, TX, USA.
7
Oncovir, Inc., Washington, D.C., USA.
8
Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA; Department of Obstetrics & Gynecology, University of Southern California, Los Angeles, CA, USA; Department of Molecular Microbiology & Immunology, University of Southern California, Los Angeles, CA, USA.

Abstract

Human papillomavirus (HPV)-mediated suppression of Langerhans cell (LC) function can lead to persistent infection and development of cervical intraepithelial neoplasia (CIN). Women with HPV-induced high-grade CIN2/3 have not mounted an effective immune response against HPV, yet it is unknown if LC-mediated T cell activation from such women is functionally impaired against HPV. We investigated the functional activation of in vitro generated LC and their ability to induce HPV16-specific T cells from CIN2/3 patients after exposure to HPV16 followed by treatment with stabilized Poly-I:C (s-Poly-I:C). LC from patients exposed to HPV16 demonstrated a lack of costimulatory molecule expression, inflammatory cytokine secretion, and chemokine-directed migration. Conversely, s-Poly-I:C caused significant phenotypic and functional activation of HPV16-exposed LC, which resulted in de novo generation of HPV16-specific CD8(+) T cells. Our results highlight that LC of women with a history of persistent HPV infection can present HPV antigens and are capable of inducing an adaptive T cell immune response when given the proper stimulus, suggesting that s-Poly-I:C compounds may be attractive immunomodulators for LC-mediated clearance of persistent HPV infection.

KEYWORDS:

HPV16; Human papillomavirus; Immune evasion; Langerhans cells

PMID:
26360252
PMCID:
PMC4658296
DOI:
10.1016/j.clim.2015.09.003
[Indexed for MEDLINE]
Free PMC Article

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