Background: Compared to younger patients on similar immunosuppression regimens, older solid organ transplant recipients experience increased rates of infection and death, but decreased rates of rejection. The mechanism behind these differences has yet to be defined, but may be related to ÒinflammagingÓ driven by CMV infection.
Objective: Evaluate older versus younger solid organ transplant recipients for CMV-specific T cell immune responses.
Methods: Peripheral blood mononuclear cells were isolated from 20 older (³ age 60) and 25 matched younger (ages 30-59) kidney transplant recipients at 3 months after transplantation. Eight recipients were high risk by CMV serology (D+/R-) and 37 were intermediate risk (D-/R+). Overlapping CMV peptide pools were used for stimulation. Intracellular staining to determine cytokine stimulation was performed by multiparameter flow cytometry. Statistical analysis was performed using Jmp Pro 11 software.
Results: There was no association between patient age and CMV risk status (p = 0.728). There was no difference between older and younger kidney transplant recipients in release of IFNg, TNFa, or IL-2 from CD4+ or CD8+ T cells in response to CMV antigen stimulation. However, Older recipients had similar frequencies of CD8+ nave cells but decreased frequency of CD8+ terminally differentiated effector memory CD45RA+ (TEMRA) T cells releasing both IFNg and TNFa (p = 0.037) (Figure). Interestingly, development of CMV viremia was associated with a weaker CMV-specific immune response: Patients who had a history of CMV viremia had a decreased frequency of CD8+ TEMRA cells releasing both IFNg and TNFa (p = 0.041).
Conclusion: Older kidney transplant recipients demonstrated a decreased frequency of CMV-specific polyfunctional CD8+ TEMRA T cells. This impaired memory T cell response to CMV suggests a possible mechanism for the increased vulnerability of older recipients to CMV infection or reactivation, which may in turn worsen age-related immune dysfunction. Furthermore, patients with subsequent CMV viremia had a decreased frequency of CMV-specific polyfunctional CD8+ TEMRA T cells. This finding may explain patient vulnerability to CMV viremia despite modern protocols for antiviral prophylaxis.
G. Sunga, None
E. Reed, None
J. Schaenman, None