Antigen-specific CD4 cells assist CD8 T-effector cells in eliminating keratinocytes.
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.
Broom
Jennifer K
JK
Immunology and Metabolic Medicine, The University of Queensland Diamantina Institute for Cancer, Princess Alexandra Hospital, Ipswich Road, Brisbane, Queensland, Australia.
Lew
Andrew M
AM
Azukizawa
Hiroaki
H
Kenna
Tony J
TJ
Leggatt
Graham R
GR
Frazer
Ian H
IH
D000818:Animals; D000941:Antigens / Q000276:immunology*; D019013:CD40 Antigens / Q000494:pharmacology; D004195:Disease Models, Animal; D006084:Graft Rejection / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D019382:Human Growth Hormone / Q000276:immunology / Q000378:metabolism; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology / Q000378:metabolism; D016038:Skin Transplantation / Q000276:immunology / Q000473:pathology* / Q000502:physiology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology* / Q000502:physiology; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology* / Q000502:physiology
D000941:Antigens; D019013:CD40 Antigens; D019382:Human Growth Hormone; D010047:Ovalbumin