Antigen-specific CD4 cells assist CD8 T-effector cells in eliminating keratinocytes

Broom, Jennifer K., Lew, Andrew M., Azukizawa, Hiroaki, Kenna, Tony J., Leggatt, Graham R., & Frazer, Ian H. (2010) Antigen-specific CD4 cells assist CD8 T-effector cells in eliminating keratinocytes. Journal of Investigative Dermatology, 130(6), pp. 1581-1589.

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Abstract

Keratinocytes expressing tumor or viral antigens can be eliminated by antigen-primed CD8 cytotoxic T cells. CD4 T-helper cells help induction of CD8 cytotoxic T cells from naive precursors and generation of CD8 T-cell memory. In this study, we show, unexpectedly, that CD4 cells are also required to assist primed CD8 effector T cells in rejection of skin expressing human growth hormone, a neo-self-antigen, in keratinocytes. The requirement for CD4 cells can be substituted by CD40 costimulation. Rejection of skin expressing ovalbumin (OVA), a non-self-antigen, by primed CD8 cytotoxic T cells can in contrast occur without help from antigen-specific CD4 T cells. However, rejection of OVA expressing keratinocytes is helped by antigen-specific CD4 T cells if only low numbers of primed or naive OVA-specific CD8 T cells are available. Effective immunotherapy directed at antigens expressed in squamous cancer may therefore be facilitated by induction of tumor antigen-specific CD4 helper T cells, as well as cytotoxic CD8 T cells.

Impact and interest:

7 citations in Scopus
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7 citations in Web of Science®

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ID Code: 94048
Item Type: Journal Article
Refereed: Yes
Keywords: Animals, Antigens/ immunology, Antigens, CD40/pharmacology, Disease Models, Animal, Graft Rejection/immunology/pathology/physiopathology, Human Growth Hormone/immunology/metabolism, Keratinocytes/drug effects/metabolism/ pathology, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Ovalbumin/immunology/metabolism, Skin Transplantation/immunology/ pathology/physiology, T-Lymphocytes, Cytotoxic/drug effects/ immunology/physiology, T-Lymphocytes, Helper-Inducer/drug effects/ immunology/physiology
DOI: 10.1038/jid.2010.17
ISSN: 1523-1747
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2010 The Society for Investigative Dermatology, Inc.
Deposited On: 21 Mar 2016 02:40
Last Modified: 22 Mar 2016 03:06

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