Immunosenescence increases the rate of acceptance of kidney allotransplants in elderly recipients through exhaustion of CD4+ T-cells

Trzonkowski, Piotr; Dębska‐Ślizień, Alicja; Jankowska, Magdalena; Wardowska, Anna; Carvalho-Gaspar, Manuela; Hak, Łukasz; Moszkowska, Grażyna; Bzoma, Beata; Mills, Natalie; Wood, Kathryn J.; Myśliwska, Jolanta; Rutkowski, Bolesław

doi:10.1016/j.mad.2009.12.006

Cited by 61 publications

(42 citation statements)

References 32 publications

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“…This indicates that the degree of T cell aging is not associated with the risk of infection after RTx in contrast to the association between aged T cells and a lowered risk for acute rejection (32,33). The only association we found was between the development of CMV viremia/disease in patients with a D+/RÀ configuration and the frequency of CD8 + CD28 null T cells before transplant.…”

Section: Discussioncontrasting

confidence: 72%

Uremia-Associated Premature Aging of T Cells Does Not Predict Infectious Complications After Renal Transplantation

Dedeoğlu

Meijers

Klepper

et al. 2016

American Journal of Transplantation

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Patients with end-stage renal disease have prematurely aged T cell systems. We tested whether T cell aging parameters were associated with the risk of infections after renal transplantation (RTx). We studied 188 patients over 1 year. Peripheral T cells were analyzed before and at 3 and 6 mo after RTx for frequency of recent thymic emigrants, relative telomere length and differentiation status. These parameters were related to the occurrence of opportunistic and serious infections. Overall, 84 patients developed an infection. In this group, 50 developed an opportunistic infection and 53 developed a serious infection. T cell aging parameters assessed before RTx were not associated with infection risk. The memory T cells showed a decrease within the first 3 mo in both groups (p < 0.001). The CD4 + memory T cells increased between 3 and 6 mo within the infection group (p = 0.015). The number of CD8 + memory T cells increased in both groups (p < 0.001) but reached baseline levels only in the infection group. In the infection group, the CD8 + CD28null T cell percentage increased between 3 and 6 mo (p = 0.024), tending to be higher than at baseline (p = 0.061). These differences in post-RTx dynamics resulted from infections. Parameters of uremia-associated premature aging of peripheral T cells do not predict posttransplant infections.

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Section: Discussioncontrasting

confidence: 72%

Uremia-Associated Premature Aging of T Cells Does Not Predict Infectious Complications After Renal Transplantation

Dedeoğlu

Meijers

Klepper

et al. 2016

American Journal of Transplantation

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“…Interestingly, CMV infection after LTx is associated with an increased predisposition to develop opportunistic infections (52). Second, immune senescence has been associated with improved kidney allograft survival (53). Third, the majority of CD8 + CD244 + T cells in our patients belong to the Temra subset, and accumulation of circulating CD8 + Temras recently was shown to be associated with a lower risk for acute rejection after kidney transplantation (41).…”

Section: Discussionmentioning

confidence: 82%

Cytomegalovirus-Induced Expression of CD244 after Liver Transplantation Is Associated with CD8+ T Cell Hyporesponsiveness to Alloantigen

Mare-Bredemeijer

Shi

Mancham

et al. 2015

The Journal of Immunology

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The chronic presence of viral Ags can induce T cell exhaustion, which is characterized by upregulation of coinhibitory receptors and loss of T cell function. We studied whether a similar phenomenon occurs after liver transplantation (LTx), when there is continuous exposure to alloantigen. Expression of coinhibitory receptors on circulating CD4+ and CD8+ T cells was analyzed longitudinally in 19 patients until 6 mo after LTx and cross-sectionally in 38 patients late (1–12 y) after LTx. Expression of the coinhibitory receptors CD160 and CD244 on circulating CD8+ T cells was already higher 6 mo after LTx compared with pre-LTx, and the elevated expression was sustained late after LTx, with CD244 showing the more prominent increase. The strongest upregulation of CD244 on circulating CD8+ T cells was observed in patients who experienced CMV infection after LTx. CMV infection also was associated with reduced CD8+ T cell proliferation and cytotoxic degranulation in response to alloantigen late after LTx. Purified CD244+CD8+ T cells from LTx patients showed lower proliferative responses to alloantigen, as well as to polyclonal stimulation, than did their CD244− counterparts. In addition, the CD244+CD8+ T cell population contained the majority of CMV peptide–loaded MHC class I tetramer-binding cells. In conclusion, CMV infection after LTx, rather than persistence of alloantigen, induces the accumulation of dysfunctional CD244+CD8+ T cells in the circulation that persist long-term, resulting in reduced frequencies of circulating alloreactive CD8+ T cells. These results suggest that CMV infection restrains CD8+ T cell alloresponses after LTx.

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“…However, a causal relationship between age-related changes of circulating T cells and age-related impaired immunity has only been implicated by association of these findings (14,15). To our knowledge, only one recent study, including a small series of kidney transplant patients, indicated that elderly patients with ESRD with a relatively less differentiated T-cell system are at a higher risk for AR (16).…”

Section: * 2012 Lippincott Williams and Wilkinsmentioning

confidence: 99%

Terminally Differentiated CD8+ Temra Cells Are Associated With the Risk for Acute Kidney Allograft Rejection

Betjes

Meijers²,

Wit³

et al. 2012

Transplantation

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Immunosenescence increases the rate of acceptance of kidney allotransplants in elderly recipients through exhaustion of CD4+ T-cells

Cited by 61 publications

References 32 publications

Uremia-Associated Premature Aging of T Cells Does Not Predict Infectious Complications After Renal Transplantation

Uremia-Associated Premature Aging of T Cells Does Not Predict Infectious Complications After Renal Transplantation

Cytomegalovirus-Induced Expression of CD244 after Liver Transplantation Is Associated with CD8+ T Cell Hyporesponsiveness to Alloantigen

Terminally Differentiated CD8+ Temra Cells Are Associated With the Risk for Acute Kidney Allograft Rejection

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