Human growth hormone presented by K14hGH-transgenic skin grafts induces a strong immune response but no graft rejection

Zhong, Jie, Matsumoto, Koji, De Kluyver, Rachel, Fernando, Germain J. P., Leggatt, Graham R. and Frazer, Ian H. (2004) Human growth hormone presented by K14hGH-transgenic skin grafts induces a strong immune response but no graft rejection. Immunology and Cell Biology, 82 6: 577-586. doi:10.1111/j.1440-1711.2004.01292.x


Author Zhong, Jie
Matsumoto, Koji
De Kluyver, Rachel
Fernando, Germain J. P.
Leggatt, Graham R.
Frazer, Ian H.
Title Human growth hormone presented by K14hGH-transgenic skin grafts induces a strong immune response but no graft rejection
Journal name Immunology and Cell Biology   Check publisher's open access policy
ISSN 0818-9641
1440-1711
Publication date 2004-01-01
Sub-type Article (original research)
DOI 10.1111/j.1440-1711.2004.01292.x
Volume 82
Issue 6
Start page 577
End page 586
Total pages 10
Place of publication London, United Kingdom
Publisher Nature
Language eng
Abstract Although immune responses leading to rejection of transplantable tumours have been well studied, requirements for epithelial tumour rejection are unclear. Here, we use human growth hormone (hGH) expressed in epithelial cells (skin keratinocytes) as a model neo-self antigen to investigate the consequences of antigen presentation from epithelial cells. Mice transgenic for hGH driven from the keratin 14 promoter express hGH in skin keratinocytes. This hGH-transgenic skin is not rejected by syngeneic non-transgenic recipients, although an antibody response to hGH develops in grafted animals. Systemic immunization of graft recipients with hGH peptides, or local administration of stimulatory anti-CD40 antibody, induces temporary macroscopic graft inflammation, and an obvious dermal infiltrate of inflammatory cells, but not graft rejection. These results suggest that a neo-self antigen expressed in somatic cells in skin can induce an immune response that can be enhanced further by induction of specific immunity systemically or non-specific immunity locally. However, immune responses do not always lead to rejection, despite induction of local inflammatory changes. Therefore, in vitro immune responses and in vivo delayed type hypersensitivity are not surrogate markers for immune responses effective against epithelial cells expressing neoantigens.
Keyword Human growth hormone (hGH)
Keratinocyte
Tolerance
Transplantation
Tumour immunology
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

 
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Created: Wed, 15 Aug 2007, 14:08:18 EST