Helper requirements for generation of effector CTL to islet beta cell antigens.
We have dissected the helper requirements for converting a tolerogenic CD8 T cell response into one capable of causing destruction of the pancreatic islets. Injection of naive OVA-specific CD8 T cells into transgenic mice expressing OVA in the pancreas only resulted in islet destruction when activated CD4 Th cells were coinjected. This requirement for activated CD4 T cell help for induction of primary CD8 T cell-mediated immunity to tissue Ags contrasts recent reports suggesting that help is only important for CTL memory. Our findings show that signaling of CD40 on the dendritic cell presenting to CD8 T cells is important, but not sufficient, for induction of diabetes. Furthermore, once helpers are activated, they need not recognize Ag on the dendritic cells they license. This provides insight into the helper requirements for adoptive transfer immunotherapy of tumors and suggests key points for inhibition of CTL-mediated autoimmunity.
Behrens
Georg M N
GM
Immunology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia. health@wehi.edu.au
Li
Ming
M
Davey
Gayle M
GM
Allison
Janette
J
Flavell
Richard A
RA
Carbone
Francis R
FR
Heath
William R
WR
D019264:Adoptive Transfer; D000818:Animals; D017951:Antigen Presentation / Q000235:genetics; D001324:Autoantigens / Q000502:physiology*; D023201:CD40 Ligand / Q000235:genetics / Q000502:physiology; D002450:Cell Communication / Q000235:genetics / Q000276:immunology*; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000276:immunology / Q000473:pathology; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007515:Islets of Langerhans / Q000276:immunology* / Q000473:pathology*; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000637:transplantation; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism
D001324:Autoantigens; D018984:Epitopes, T-Lymphocyte; D000949:Histocompatibility Antigens Class II; D023201:CD40 Ligand; D010047:Ovalbumin