How immunosuppressive therapy affects T cells from kidney transplanted patients of different age: the role of latent cytomegalovirus infection

Abstract

SummaryThe average age of patients receiving renal transplantation is increasing as programmes have been established which support the donation of organs from elderly donors to older recipients. Little is known about the effect of immunosuppressive therapy on the immune system of older patients. In this study, T cell function and the composition of the T cell repertoire were analysed in immunosuppressed renal transplant recipients of different age and cytomegalovirus (CMV) status in comparison to age-and CMV-matched controls. Independent of age and CMV status, the production of interleukin (IL)-2 and interferon (IFN)-γ by T cells was decreased in the patient groups and autologous serum from patients was capable of inhibiting the proliferation of CD3 + T cells. CXCR5 expression on T cells was increased in patients versus controls reflecting reduced endogenous IL-2 signalling under immunosuppressive therapy. In CMV-seronegative patients kidney transplantation and immunosuppressive therapy did not induce changes in the CD8+ T cell pool, but there was a moderate increase in CD4 + CD28 − effector T cells when compared to age-matched controls. In contrast, latent CMV infection triggered a shift from early to late differentiated CD4 + and CD8 + T cells in patients and controls. This shift was most pronounced in elderly transplant patients under immunosuppressive therapy. In conclusion, our results demonstrate that immunosuppressive therapy following kidney transplantation is effective in patients older than 65 years. Latent CMV infection, however, accelerates age-related changes in the T cell repertoire in elderly people under immunosuppressive therapy. These patients should therefore be monitored with special care.

The Effect of Induction Therapy on Established CMV Specific T Cell Immunity in Living Donor Kidney Transplantation

“…Pearl et al (2005) revealed that residual T cells after depletion therapy share a single phenotype corresponding with effector memory T cells (CD3+CD4+CD45RA-CD62L-CCR7-), the study suggested that effector memory T cells are selectively resistant to the therapeutic depletion therapy. In contrast to this, other parts of adaptive immune system (CD4+, CD8+, IgG) are thoroughly influenced by post-transplant immunosuppression (Carter et al 2006, Gurkan et al 2010, Zand et al 2005 and therefore it is possible that homeostatic proliferation of T cells were not detected in our 2 time-points study.…”

“…The superior outcome of kidney transplantation is usually reached in LD (living donor) recipients, mainly due to shorter dialysis time and younger recipient age. Recently, T cell repertoire has also been described to be age-dependent in patients under immunosuppressive therapy (Welzl et al 2014). Similarly, the long term dialysis is associated with the premature aging of immune system (Betjes 2013).…”

Decreased frequency of Th22 cells and IL-22 cytokine in kidney transplant patients with active cytomegalovirus infection

“…It may also bring to mind that the reduction in these cells in HCMV + patients could be due to immunosuppression therapy that transplanted patients received. It is evident that immunosuppression affects the frequency and composition of CD4 + T cell subsets, including a reduction in the IFN-γ producing Th1 and circulating follicular regulatory T cells (cTfr) [ 40 , 41 ]. To the best of our knowledge, the effect of immunosuppressive drugs on Th22 cells and cytokine has not been studied well.…”

Risk factors for cytomegalovirus disease in seropositive renal transplant recipients; a single-center case-controlled study

“…However, the elevated CMV seroprevalence found in our study does not support this hypothesis. On the contrary, new findings have shown that latent CMV infection accelerates age-related changes in the T cell subsets in elderly patients, leading to a reduced proportion of naïve and early memory T cells and an increased number of CD8+ effector T cells which produce gamma interferon but do not have enough growth potential, making CMV disease more probable ( 15 , 16 ). Considering the previous finding, CMV prophylaxis in kidney transplant recipients older than 55 years might be beneficial.…”