Primary Cytomegalovirus Infection Significantly Impacts Circulating T Cells in Kidney Transplant Recipients

Meijers, Ruud W. J.; Litjens, Nicolle H.R.; Hesselink, Dennis A.; Langerak, Anton W.; Baan, Carla C.; Betjes, Michiel G. H.

doi:10.1111/ajt.13396

Cited by 29 publications

(26 citation statements)

References 44 publications

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“…This subset highly expressed endothelial homing marker CX3CR1 and exhibited cytotoxic function against endothelial cells in an NKGD2‐dependent manner. Furthermore, in concordance with a recent study on primary CMV infection post–kidney transplant , high frequency of CD4+CD28‐negative population was associated with decline in eGFR at 1 year posttransplant and an increased rate of delayed graft function, though it is unclear whether this observation is related or not to direct immune injury to the graft.…”

Section: Belatacept Resistance and T Cellssupporting

confidence: 83%

CD4+ CD28-Negative Cells: Armed and Dangerous

Murakami

Riella

2016

American Journal of Transplantation

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Section: Belatacept Resistance and T Cellssupporting

confidence: 83%

CD4+ CD28-Negative Cells: Armed and Dangerous

Murakami

Riella

2016

American Journal of Transplantation

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“…Following CMV infection, populations of CD57 + T cells expand and exhibit polyfunctional responses . Similar expansions of memory T cells are observed in CMV‐seropositive patients with end‐stage renal disease or transplant recipients with primary CMV infection , but renal transplant patients have an extended life expectancy and a high burden of CMV. In this context, it is yet unclear whether intermittent CMV reactivation or latent CMV expand memory T cells with higher functionality or leads to their exhaustion, with a loss of cytotoxic activity and production of TNFα and IL‐2 .…”

Section: Introductionmentioning

confidence: 74%

CMV drives the expansion of highly functional memory T cells expressing NK‐cell receptors in renal transplant recipients

et al. 2017

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Cytomegalovirus (CMV) is a common opportunistic infection encountered in renal transplant recipients (RTRs) and may be reactivated without symptoms at any time post-transplant. We describe how active and latent CMV affect T-cell subsets in RTRs who are stable on maintenance therapy. T-cell responses to CMV were assessed in RTRs (n = 54) >2 years post-transplant, and healthy controls (n = 38). Seven RTRs had CMV DNA detectable in plasma. CMV antibody and DNA aligned with increased proportions of CD8 T cells and reduced CD4/CD8 ratios. This paralleled an expansion of effector memory T-cell (T ), terminally differentiated T-cell (T ) and CD57 T cell populations. Expression of NK-cell receptors, LIR-1 and KLRG1 on CD4 and CD8 CD57 T and T cells correlated with elevated interferon-γ and cytotoxic responses to anti-CD3 and increased cytotoxic responses to CMV phosphoprotein (pp) 65 in RTRs who carried CMV DNA. CD8 T cells from all CMV seropositive RTRs responded efficiently to CMV immediate early (IE) -1 peptides. The data show that latent and active CMV infection can alter T-cell subsets in RTRs many years after transplantation, and up-regulate T-cell expression of NK-cell receptors. This may enhance effector responses of CD4 and CD8 T cells against CMV.

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“…The different posttransplant T cell dynamics were clearly caused by the infections. The significant rise in CD8 + CD28 null T cell percentage in the infection group, for example, was most likely caused by a primary CMV infection (4,8,37). A study by Calarota et al showed that the drop in CD4 + T cells coincided with the peak of OIs (28).…”

Section: Discussionmentioning

confidence: 98%

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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Primary Cytomegalovirus Infection Significantly Impacts Circulating T Cells in Kidney Transplant Recipients

Cited by 29 publications

References 44 publications

CD4+ CD28-Negative Cells: Armed and Dangerous

CD4+ CD28-Negative Cells: Armed and Dangerous

CMV drives the expansion of highly functional memory T cells expressing NK‐cell receptors in renal transplant recipients

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

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