Evidence of Immunologic Dysfunction in Older Solid Organ Transplant Recipients

Background: The numbers of older patients with end stage organ disease requiring organ transplantation continues to grow as the population ages. However, older transplant recipients experience increased rates of infection and death as compared with younger patients.

Objective: Compare immunologic profiles in older versus younger solid organ transplant recipients.
Methods: Peripheral blood mononuclear cells were isolated from 20 older (³ age 60) and 34 matched younger (ages 30-59) kidney transplant recipients at 3 months after transplantation. Immunophenotyping was performed by multiparameter flow cytometry. Statistical analysis by Kruskal-Wallis test was performed using Jmp Pro 11; single asterisk indicates p<0.05, double asterisk p<0.01, and triple asterisk p<0.001.
Results: Older kidney transplant recipients had a statistically significantly lower frequency of na•ve CD4+ (19.1% versus 37.0% in younger patients, p=0.002) and na•ve CD8+ T cells (12.7% versus 38.3%, p<0.001) (Figure 1).

Figure 1:

 Older recipients also demonstrated an increased frequency of effector memory (EM) CD4+ (42.2 versus 22.5%, p=0.002), EM CD8+ (33.3% versus 20.4%, p<0.001), and terminally differentiated CD8+ T cells (48.7% versus 29.1%, p=0.005). Older recipients also displayed increased frequency of exhausted and senescent T cells, with increased frequency of CD57+ (30.1% versus 19.4%, p=0.02) and KLRG1+ CD8+ T cells (63.7% versus 36.3%, p<0.001) (Figure 2).

Figure 2:

In terms of innate immunity, older patients displayed increased frequency of M1 classically activated monocytes (29.9% versus 17.8%, p=0.01) and fewer M2 alternatively activated monocytes (69.1% versus 81.0%, p=0.01).
Conclusion: Compared to younger recipients, older kidney transplant recipients displayed decreased frequency of na•ve CD4+ and CD8+ T cells and increased frequency of EM CD4+ and CD8+ T cells, exhausted and senescent CD8+ T cells, and pro-inflammatory M1 monocytes, suggesting a possible mechanism for increased vulnerability to infection in the older transplant recipient. Further studies will evaluate the evolution of these changes over time and may lead to noninvasive techniques for patient monitoring, customization of immune suppression, and candidate selection based on better understanding of biologic, rather than chronologic, age.