1. ¹Department of General, Visceral, and Transplantation Surgery, Charité-Campus Virchow Clinic, Universitätsmedizin Berlin, Berlin, Germany
2. ²Institute of Medical Immunology, Charité-Campus Mitte, Universitätsmedizin Berlin, Berlin, Germany
3. ³Division of Transplant Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA

Correspondence: SG Tullius, Division of Transplant Surgery, Brigham and Women's Hospital, Harvard Medical School, 75 Francis St, Boston, Massachusetts 02115, USA. E-mail: stullius@partners.org

Received 24 March 2006; Revised 23 October 2006; Accepted 29 November 2006; Published online 31 January 2007.

Abstract

Increasing donor age is associated with reduced graft function. We wondered if donor age may not only affect intrinsic function but also alter the immune response of the recipient. Kidneys from young and old F-344 rats (3 vs 18 months) were transplanted into bilaterally nephrectomized young Lewis recipients and compared with age-matched controls (follow-up: 6 months). Renal function and structural changes were assessed serially in both native kidneys and allografts. Host alloreactivity, graft-infiltrating cells, and their inflammatory products were determined at intervals to examine the correlation of immune response and donor age. Functional and structural deterioration had advanced significantly in older allografts compared with age-matched native controls, whereas differences between young allografts and native controls of similar age were only minor. Changes in grafts from elderly rats were associated with a more intense host immune response early post-transplant (up to 1 month) reflected by significantly higher numbers of peripheral T and B cells, increased T-cell alloreactivity and modified cytokine patterns associated with elevated frequencies of intragraft dendritic cells, B cells, and CD31+ cells. By 6 months, recipients of young donor grafts produced comparable or more intense alloantigen-specific immune responses. Older donor grafts elicit a stronger immune response in the early period after transplantation.