Human growth hormone presented by K14hGH-transgenic skin grafts induces a strong immune response but no graft rejection.
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.
Zhong
Jie
J
Centre for Immunology and Cancer Research, University of Queensland, Princess Alexandra Hospital, Woolloongabba, Queensland, Australia. jzhong@cicr.uq.edu.au
Matsumoto
Koji
K
De Kluyver
Rachel
R
Fernando
Germain Jp
GJ
Leggatt
Graham R
GR
Frazer
Ian H
IH
D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D019013:CD40 Antigens / Q000276:immunology; D005260:Female; D006084:Graft Rejection / Q000276:immunology*; D006085:Graft Survival; D013006:Growth Hormone / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007114:Immunization; D007167:Immunotherapy; D051379:Mice; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic / Q000235:genetics*; D016038:Skin Transplantation / Q000276:immunology*; D014180:Transplantation
D000906:Antibodies; D019013:CD40 Antigens; D013006:Growth Hormone