Human papillomavirus 16-associated cervical intraepithelial neoplasia in humans excludes CD8 T cells from dysplastic epithelium Journal Article
| Authors: | Trimble, C. L.; Clark, R. A.; Thoburn, C.; Hanson, N. C.; Tassello, J.; Frosina, D.; Kos, F.; Teague, J.; Jiang, Y.; Barat, N. C.; Jungbluth, A. A. |
| Article Title: | Human papillomavirus 16-associated cervical intraepithelial neoplasia in humans excludes CD8 T cells from dysplastic epithelium |
| Abstract: | High-grade cervical dysplasia caused by human papillomavirus (HPV) type 16 is a lesion that should be susceptible to an HPV-specific immune response; disease initiation and persistence is predicated on expression of two viral Ags, E6 and E7. In immunecompetent subjects, at least 25% of HPV16+ high-grade cervical dysplasia lesions undergo complete regression. However, in the peripheral blood, naturally occurring IFN-γ T cell responses to HPV E6 and E7 are weak, requiring ex vivo sensitization to detect, and are not sufficiently sensitive to predict regression. In this study, we present immunologic data directly assessing cervical lymphocytes from this cohort. We found that nearly all cervical tissue T cells express the mucosal homing receptor, α4β7 surface integrin. T cells isolated from dysplastic mucosa were skewed toward a central memory phenotype compared with normal mucosal resident T cells, and dysplastic lesions expressed transcripts for CCL19 and CCL21, raising the possibility that the tissue itself sustains a response that is not detectable in the blood. Moreover, lesion regression in the study window could retrospectively be predicted at study entry by the ability of CD8+ T cells to gain access to lesional epithelium. Vascular endothelial expression of mucosal addressin cell adhesion molecule-1, the ligand that supports entry of α4β 7+ T cells into tissues, colocalized tightly with the distribution of CD8 T cells and was not expressed in persistent dysplastic epithelium. These findings suggest that dysregulated expression of vascular adhesion molecules plays a role in immune evasion very early in the course of HPV disease. Copyright © 2010 by The American Association of Immunologists, Inc. |
| Keywords: | controlled study; human tissue; protein expression; retrospective studies; unclassified drug; human cell; prospective studies; cd8+ t lymphocyte; cd8-positive t-lymphocytes; phenotype; disease association; cohort studies; cohort analysis; vascular endothelium; endothelium, vascular; cell isolation; cell movement; epithelial cells; cellular distribution; repressor proteins; integrin; cell homing; vulvar neoplasms; uterine cervix dysplasia; uterine cervix carcinoma in situ; cervical intraepithelial neoplasia; papillomavirus infections; uterine cervical dysplasia; virus virulence; secondary lymphoid tissue chemokine; homing receptor; integrin alpha4beta7; macrophage inflammatory protein 3beta; mucosal addressin cell adhesion molecule 1; human papillomavirus type 16; uterine cervix epithelium; human papillomavirus 16; integrin alpha4; integrin beta chains; oncogene proteins, viral; papillomavirus e7 proteins |
| Journal Title: | Journal of Immunology |
| Volume: | 185 |
| Issue: | 11 |
| ISSN: | 0022-1767 |
| Publisher: | The American Association of Immunologists, Inc |
| Date Published: | 2010-12-01 |
| Start Page: | 7107 |
| End Page: | 7114 |
| Language: | English |
| DOI: | 10.4049/jimmunol.1002756 |
| PUBMED: | 21037100 |
| PROVIDER: | scopus |
| PMCID: | PMC3075978 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 1" - "Export Date: 20 April 2011" - "CODEN: JOIMA" - "Source: Scopus" |
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