Aging Augments IL‐17 T‐Cell Alloimmune Responses

• Published in: American journal of transplantation Vol. 9; no. 1; pp. 54 - 63
• Main Authors: Tesar, B. M., Du, W., Shirali, A. C., Walker, W. E., Shen, H., Goldstein, D. R.
• Format: Journal Article
• Language: English
• Published: Malden, USA Blackwell Publishing Inc 01-01-2009; Wiley
• Subjects: Aging; Aging - immunology; Animals; Biological and medical sciences; CD4+ memory T cell; CD4-Positive T-Lymphocytes - immunology; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; Graft Rejection - immunology; IL‐17; Immunologic Memory; Interleukin-17 - immunology; Lymphocyte Activation; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Inbred CBA; Skin Transplantation - immunology; Spleen - cytology; Spleen - immunology; Spleen - metabolism; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Senescence; CD4 T lymphocyte; Immune response; Ageing; Cellular immunity; Interleukin 17; Allogeneic system; Memory lymphocyte; Isoimmunization; T-Lymphocyte; CD4+ memory T cell; IL-17; Aging; Age
• ISSN: 1600-6135; 1600-6143
• DOI: 10.1111/j.1600-6143.2008.02458.x

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‐γ, 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.
Aged mice exhibit elevated CD4+ memory alloimmune responses as compared to young mice, which contributes to the tempo of acute allograft rejection.