title: Aging augments IL-17 T-cell alloimmune responses.
abstract: As increasing numbers of elderly patients require solid organ transplantation, the need to better understand how aging modifies alloimmune responses increases. Here, we examined whether aged mice exhibit augmented, donor-specific memory responses prior to transplantation. We found that elevated donor-specific IL-17, but not IFN-gamma, responses were observed in aged mice compared to young mice prior to transplantation. Further characterization of the heightened IL-17 alloimmune response with aging demonstrated that memory CD4(+) T cells were required. Reduced IL-2 alloimmune responses with age contributed to the elevated IL-17 phenotype in vitro, and treatment with an anti-IL-17 antibody delayed the onset of acute allograft rejection. In conclusion, aging leads to augmented, donor-specific IL-17 immune responses that are important for the timing of acute allograft rejection in aged recipients. IL-17 targeting therapies may be useful for averting transplant rejection responses in older transplant recipients.
authors.affiliation: Department of Internal Medicine, Yale University School of Medicine, Yale University, New Haven, CT, USA.
authors.forename: B M
authors.initials: BM
authors.lastname: Tesar
authors.forename: W
authors.initials: W
authors.lastname: Du
authors.forename: A C
authors.initials: AC
authors.lastname: Shirali
authors.forename: W E
authors.initials: WE
authors.lastname: Walker
authors.forename: H
authors.initials: H
authors.lastname: Shen
authors.forename: D R
authors.initials: DR
authors.lastname: Goldstein
mesh_terms: D000375:Aging / Q000276:immunology*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006084:Graft Rejection / Q000276:immunology; D007156:Immunologic Memory; D020381:Interleukin-17 / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D016038:Skin Transplantation / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism
chemical_list: D020381:Interleukin-17