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2016 DEPARTMENT OF MEDICINE RESEARCH DAY
Title of Poster: Evidence of Immunologic Dysfunction in Older Solid Organ Transplant
Recipients
Presenter: Joanna Schaenman
Division: Infectious Diseases
☒ Faculty ☐ Fellow ☐ Resident ☐ Post-doc Research Fellow ☐ Graduate Student ☐ Medical Student ☐Other
Principal Investigator/Mentor: Joanna Schaenman Co-Investigators: Emily Liang, Yael Korin, Tiffany Sidwell,
Victoria Groysberg, Maura Rossetti, Gabriel Danovitch, Suphamai Bunnapradist, Phuong-Thu Pham, Edward Hunag, Erik
Lum, Arun Karlamangla, Elaine Reed
Thematic Poster Category:
Atherosclerosis
Infections, Injury and Repair, Inflammation, Host Defense, Immunology, Hemostasis and
Abstract
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.
Methods: Peripheral blood mononuclear cells were isolated from 20 older (≥age 60) and 34 matched
younger (ages 30-59) kidney transplant recipients 3 months post-transplantation.
Immunophenotyping was performed by multiparameter flow cytometry. Statistical analysis was by
Kruskal-Wallis test (Jmp Pro 11); single asterisk indicates p<0.05, triple asterisk, p<0.001.
Results: Older kidney transplant recipients had a lower frequency of naive CD4+ (19.1% versus
37.0% in younger patients, p=0.002) and naive CD8+ T cells (12.7% versus 38.3%, p<0.001). Older
recipients demonstrated an increased frequency of effector memory (EM) CD8+ (33.3% versus
20.4%, p<0.001) and terminally differentiated CD8+ T cells (48.7% versus 29.1%, p=0.005).
Strikingly, 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) (see Figure).
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 naive CD4+ and CD8+ T cells, and increased frequency of EM, terminally differentiated,
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
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.