Background: Over the past decade, the proportion of patients over the age of 65, both, waiting for and receiving transplants has increased dramatically. It is known that CD8+ T cells play an important role in response to an allograft and studies have shown compromised CD8+ T cell responses in parallel to increasing age. Outside transplantation numerous studies have shown a decline in reactivity of CD8+ T cells in parallel to age, however very little is known about the role of effector/memory CD8+ T cells during an alloimmune response in older organ transplant recipients.

Objective: We aim to identify the impact of aging on CD8+ T cell alloimmune response and solid organ transplantation.

Methods: Using a fully allogeneic mouse skin transplant model, we investigated the role of CD8+ T cells and allograft survival in an age-dependent manner.

Results: Our findings showed that allograft survival was significantly prolonged in older recipients with a significant increase of CD4+ and CD8+CD44highCD62Llow effector/memory T cells. However, MLR and ELISpot results demonstrated a reduced systemic inflammation of older recipients with decreased T cell proliferation and IFNg production. Upon specific TCR activation, isolated CD8+ T cells from old recipients produced lower levels of IFNg and higher levels of IL-2 when compared to young recipients that was associated with a downregulation of CD122. Finally, CBA RAG-1-/- mice reconstituted with CD8+tgTCR+ T cells from old BM3.3 mice demonstrated significantly prolonged graft survival over mice adoptively transferred with CD8+ T cells from young BM3.3 animals.

Conclusion: Older CD8+ T cells play a key role in organ transplant rejection and demonstrate a compromised functional capacity with reduced systemic inflammation and delayed allograft rejection.

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