Epithelial expression of human papillomavirus type 16 E7 protein results in peripheral CD8 T-cell suppression mediated by CD4(+)CD25(+) T cells

Narayan, S., Choyce, A., Linedale, R., Saunders, N. A., Dahler, A., Chan, E., Fernando, G. J., Frazer, I. H. and Leggatt, G. R. (2009) Epithelial expression of human papillomavirus type 16 E7 protein results in peripheral CD8 T-cell suppression mediated by CD4(+)CD25(+) T cells. European Journal of Immunology, 39 2: 481-490. doi:10.1002/eji.200838527


Author Narayan, S.
Choyce, A.
Linedale, R.
Saunders, N. A.
Dahler, A.
Chan, E.
Fernando, G. J.
Frazer, I. H.
Leggatt, G. R.
Title Epithelial expression of human papillomavirus type 16 E7 protein results in peripheral CD8 T-cell suppression mediated by CD4(+)CD25(+) T cells
Journal name European Journal of Immunology   Check publisher's open access policy
ISSN 0014-2980
Publication date 2009-02
Year available 2009
Sub-type Article (original research)
DOI 10.1002/eji.200838527
Volume 39
Issue 2
Start page 481
End page 490
Total pages 10
Editor F. Y. Liew
Place of publication Germany
Publisher Wiley- VCH Verlag
Collection year 2010
Language eng
Subject C1
970106 Expanding Knowledge in the Biological Sciences
970111 Expanding Knowledge in the Medical and Health Sciences
920108 Immune System and Allergy
920102 Cancer and Related Disorders
110709 Tumour Immunology
111201 Cancer Cell Biology
Abstract The role of thymic versus peripheral epithelium in the regulation of the antigen-specific CD8 T-cell repertoire is still largely unresolved, We generated TCR-beta chain transgenic mice in which an increased frequency of peripheral CD8 T cells recognizes an epitope from a viral oncoprotein (HPV16E7) in the context of H-2D(b) MHC class I. When T cells from these mice developed through the thymus of mice expressing functional E7 protein from a keratin 14 promoter, no major perturbation to transgenic T-cell development in the thymus was observed in these double-transgenic mice. In contrast, peripheral CD8 T-cell responses in the single-transgenic, K14E7 mice, including those unrelated to E7 antigen, are reduced whereas CD4 T-cell responses and antibody production are unchanged in these mice. Peripheral non-responsiveness among CD8 T cells was mediated largely by CD4(+)CD25(+) T cells. This suggested that epithelium expressing HPV16E7 protein induces Treg that specifically down-regulate CD8 T-cell responses in the periphery. This may have important consequences for the treatment of cervical pre-cancers and provides a model for understanding differential suppression of T and B lymphocyte subsets by Treg.
Keyword Skin
Class-I molecules
Q-Index Code C1
Q-Index Status Confirmed Code

 
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Created: Thu, 03 Sep 2009, 08:45:57 EST by Mr Andrew Martlew on behalf of UQ Diamantina Institute