Immunosenescence in renal transplantation: a changing balance of innate and adaptive immunity

Abstract

Purpose of review: With global demographic changes and an overall improved healthcare, more older end-stage renal disease (ESRD) patients receive kidney transplants. At the same time, organs from older donors are utilized more frequently. Those developments have and will continue to impact allocation, immunosuppression and efforts improving organ quality.

Recent findings: Findings mainly outside the field of transplantation have provided insights into mechanisms that drive immunosenescence and immunogenicity, thus providing a rationale for an age-adapted immunosuppression and relevant clinical trials in the elderly. With fewer rejections in the elderly, alloimmune responses appear to be characterized by a decline in effectiveness and an augmented unspecific immune response.

Summary: Immunosenescence displays broad and ambivalent effects in elderly transplant recipients. Those changes appear to compensate a decline in allospecific effectiveness by a shift towards an augmented unspecific immune response. Immunosuppression needs to target those age-specific changes to optimize outcomes in elderly transplant recipients.

Figure 1

Concept of a less effective allospecific but augmented unspecific immune response in the elderly. (a) T cell subsets in the healthy individuals. (b) Old CD4⁺ T cell with diminished alloresponse potential, including an impaired IL-2 capacity and CD28 downregulation coincide with an increasing NK cell receptor equipment [,–54]. (c) Enhanced cytotoxic capacity of old CD28⁻ CD8⁺ T cells that upregulate CD57 while co-expressing NK cell receptors [43,44].