High numbers of differentiated CD28null CD8+ T cells are associated with a lowered risk for late rejection and graft loss after kidney transplantation

Betjes, M.; Litjens, Nicolle H.R.

doi:10.1371/journal.pone.0228096

Cited by 14 publications

(14 citation statements)

References 31 publications

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“…40 Another study that examined the composition of the peripheral immune compartment in adult kidney transplant recipients reported higher percentages of naïve CD8 T cells in patients experiencing biopsy-proven late rejection; a similar trend was seen in the abundance of CD8 CM T cells. 41 The relationship between abundance of naïve CD8 T cells, CD8 CM T cells and allograft health demonstrated here further underscore the importance of these cell types in the pathogenesis of rejection.…”

Section: Discussionsupporting

confidence: 51%

High-dimensional profiling of pediatric immune responses to solid organ transplantation

Rao

Amouzgar

Harden

et al. 2022

Preprint

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Solid organ transplant remains a life-saving therapy for children with end-stage heart, lung, liver, or kidney disease; however, ~25% of allograft recipients experience acute rejection within the first 12 months after transplant. Our ability to detect rejection early and to develop less toxic immunosuppressive agents is hampered by an incomplete understanding of the immune changes associated with rejection, particularly in the pediatric population. Here we used high-dimensional single-cell proteomic technologies (CyTOF) to generate the first detailed, multi-lineage analysis of the peripheral blood immune composition of pediatric solid organ transplant recipients. We report that the organ transplanted impacts the immune composition post-transplant. When taking these allograft-specific differences into account, we further observed that differences in the proportion of subsets of CD8 and CD4 T cells were significantly associated with allograft health. Together, these data form the basis for mechanistic studies into the pathobiology of rejection to develop less invasive tools to identify early rejection and new immunosuppressive agents with greater specificity and less toxicity.

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Section: Discussionsupporting

confidence: 51%

High-dimensional profiling of pediatric immune responses to solid organ transplantation

Rao

Amouzgar

Harden

et al. 2022

Preprint

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“…While CD8 + T cells are known to be important in controlling CMV and preventing associated disease in transplant recipients ( 50 – 53 ) and immunocompetent individuals ( 5 ), there have been inconsistent reports on the relationship between CD28 – CD8 + T cells and kidney transplant outcomes ( 15 , 16 , 54 , 55 ). This study highlighted a protective role for these terminally differentiated CD8 + T cells in resolution of CMV viremia where greater numbers of CD28 – CD8 + T cells and expression of inhibitory and NK-like receptors on these cells were associated with effective control of viremia in CMV PCR + patients.…”

Section: Discussionmentioning

confidence: 99%

NK and CD8+ T cell phenotypes predict onset and control of CMV viremia after kidney transplant

Pickering¹,

Sen²,

Arakawa-Hoyt³

et al. 2021

JCI Insight

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Cytomegalovirus (CMV) causes mostly asymptomatic but lifelong infection. Primary infection or reactivation in immunocompromised individuals can be life-threatening. CMV viremia often occurs in solid organ transplant (SOT) recipients and associates with decreased graft survival and higher mortality. Furthering understanding of impaired immunity allowing CMV reactivation is critical to guiding anti-viral therapy and examining CMV's impact on outcomes of SOT. This study characterized longitudinal immune responses to CMV in 31 kidney transplant recipients with CMV viremia and matched, non-viremic recipients. Subjects were sampled three-and twelve-months post-transplant, with additional samples oneweek and one-month post-viremia. Peripheral blood mononuclear cells (PBMC) were stained for NK and T cell markers. PBMC transcriptomes were characterized by RNA-Seq. Plasma proteins were quantified by Luminex. CD8 T cell transcriptomes were characterized by single-cell RNA-Seq. Pre-viremia, patients had high levels of IL-15 with concurrent expansion of immature CD56 bright NK cells. Post-viremia, mature CD56 dim NK cells and CD28 -CD8 T cells upregulating inhibitory and NK-associated receptors were expanded. Memory NK cells and NK-like CD28 -CD8 T cells were associated with control of viremia. These findings suggest signatures of innate activation may be prognostic for CMV reactivation posttransplant, while CD8 T cell functionality is critical for effective control of CMV.

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“…In kidney transplantation recipients, the expansion of highly differentiated memory CD8 T cells is associated with an increased risk of skin cancer [92] and less risk for both early acute and late rejection [93][94][95]. It can be expected that the loss of TCR repertoire in premature ageing associates with a higher risk for certain infections, but this has not been studied yet.…”

Section: Premature Ageing Of the Adaptive Immune System And Clinical mentioning

confidence: 99%

Uremia-Associated Ageing of the Thymus and Adaptive Immune Responses

Betjes

2020

Toxins

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Progressive loss of renal function is associated with a series of changes of the adaptive immune system which collectively constitute premature immunological ageing. This phenomenon contributes significantly to the mortality and morbidity of end-stage renal disease (ESRD) patients. In this review, the effect of ESRD on the T cell part of the adaptive immune system is highlighted. Naïve T cell lymphopenia, in combination with the expansion of highly differentiated memory T cells, are the hallmarks of immunological ageing. The decreased production of newly formed T cells by the thymus is critically involved. This affects both the CD4 and CD8 T cell compartment and may contribute to the expansion of memory T cells. The expanding populations of memory T cells have a pro-inflammatory phenotype, add to low-grade inflammation already present in ESRD patients and destabilize atherosclerotic plaques. The effect of loss of renal function on the thymus is not reversed after restoring renal function by kidney transplantation and constitutes a long-term mortality risk factor. Promising results from animal experiments have shown that rejuvenation of the thymus is a possibility, although not yet applicable in humans.

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High numbers of differentiated CD28null CD8+ T cells are associated with a lowered risk for late rejection and graft loss after kidney transplantation

Cited by 14 publications

References 31 publications

High-dimensional profiling of pediatric immune responses to solid organ transplantation

High-dimensional profiling of pediatric immune responses to solid organ transplantation

NK and CD8+ T cell phenotypes predict onset and control of CMV viremia after kidney transplant

Uremia-Associated Ageing of the Thymus and Adaptive Immune Responses

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