The Role of Macrophage Lineage Cells in Kidney Graft Rejection and Survival

Rowshani, Ajda T.; Vereyken, Elly J. F.

doi:10.1097/tp.0b013e318250c10f

Cited by 43 publications

(39 citation statements)

References 116 publications

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“…Interferon-γ produced by CD4 + T cells, along with tumor necrosis factor from antigen-presenting cells, can induce classically activated macrophages, which secrete interleukin-1 (IL-1), IL-6, IL-12, IL-18, and IL-23 (36). Activated macrophages during acute rejection promote inflammation and induce tissue damage by secreting a large number of cytokines, nitric oxide, and superoxide (37). Although multiple cell types infiltrated renal allografts, macrophage infiltration was associated with renal allograft dysfunction (638) and renal tubular stress, as indicated by HLA-DR expression, while T cell infiltration was not (6).…”

Section: Discussionmentioning

confidence: 99%

Increased Circulating T Lymphocytes Expressing HLA-DR in Kidney Transplant Recipients with Microcirculation Inflammation

et al. 2017

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We consecutively enrolled 82 kidney transplant recipients (KTRs) with stable renal function and 24 KTRs who underwent indication biopsy to compare the histological grading of renal allografts with the activity of circulating T lymphocyte subsets and monocytes determined by flow cytometry, which were obtained at 2 weeks after kidney transplantation (KT) and at the time of indication biopsy, respectively. The sum of the scores of glomerulitis (g) + peritubular capillaritis (ptc), inflammation (i) + tubulitis (t), interstitial fibrosis (ci) + tubular atrophy (ct), and fibrointimal thickening (cv) + arteriolar hyaline thickening (ah) was used to assign a histological grade to the renal allograft samples. The frequencies of CD4+HLA-DR+/CD4+ T cells and CD8+HLA-DR+/CD8+ T cells were significantly increased in KTRs with a microcirculation inflammation (MI) sum score ≥ 1 when compared with KTRs with an MI sum score = 0 as well as stable KTRs. In these 2 subsets, only CD4+HLA-DR+/CD4+ T cells were positively correlated with MI sum scores. Analysis using the receiver operating characteristic (ROC) curve showed that antibody-mediated rejection (AMR) could be predicted with a sensitivity of 80.0% and a specificity of 94.7%, using a cutoff value of 29.6% frequency of CD4+HLA-DR+/CD4+ T cells. MI was significantly associated with an increased frequency of activated T lymphocytes expressing human leukocyte antigen-antigen D related (HLA-DR). Further studies should focus on validating the utility of circulating CD4+HLA-DR+/CD4+ T cells as a noninvasive, immunologic monitoring tool for the prediction of AMR.

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Section: Discussionmentioning

confidence: 99%

Increased Circulating T Lymphocytes Expressing HLA-DR in Kidney Transplant Recipients with Microcirculation Inflammation

et al. 2017

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“…MΦs can be detected in large numbers in kidney grafts undergoing ischemia/reperfusion injury, during T–cell and antibody–mediated rejection. MΦ infiltration correlated with poor rejection prognosis due to their contribution to early and late inflammatory injury [8], [9]. Depletion of infiltrating MΦs reduced histological features of acute rejection and led to improvement of transplant function in rodent models of kidney transplantation (Tx) [10], [11].…”

Section: Introductionmentioning

confidence: 99%

A Shift towards Pro-Inflammatory CD16+ Monocyte Subsets with Preserved Cytokine Production Potential after Kidney Transplantation

et al. 2013

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BackgroundThe presence of monocyte-macrophage lineage cells in rejecting kidney transplants is associated with worse graft outcome. At present, it is still unclear how the monocyte-macrophage related responses develop after transplantation. Here, we studied the dynamics, phenotypic and functional characteristics of circulating monocytes during the first 6 months after transplantation and aimed to establish the differences between kidney transplant recipients and healthy individuals.MethodsPhenotype, activation status and cytokine production capacity of classical (CD14++CD16−), intermediate (CD14++CD16+) and non-classical (CD14+CD16++), monocytes were determined by flow cytometry in a cohort of 33 healthy individuals, 30 renal transplant recipients at transplantation, 19 recipients at 3 months and 16 recipients at 6 months after transplantation using a cross-sectional approach.ResultsThe percentage of both CD16+ monocyte subsets was significantly increased in transplant recipients compared to healthy individuals, indicative of triggered innate immunity (p≤0.039). Enhanced production capacity of tumor necrosis factor-α, interferon-γ and interleukin-1β was observed by monocytes at transplantation compared to healthy individuals. Remarkably, three months post-transplant, in presence of potent immunosuppressive drugs and despite improved kidney function, interferon-γ, tumor necrosis factor-α and interleukin-10 production capacity still remained significantly increased.ConclusionOur data demonstrate a skewed balance towards pro-inflammatory CD16+ monocytes that is present at the time of transplantation and retained for at least 6 months after transplantation. This shift could be one of the important drivers of early post-transplant cellular immunity.

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“…Recently, the contribution of regulatory T cells and antigen-presenting cells as potential modifiers of the allograft response has attracted much attention (2), whereas the role of macrophages has received relatively little attention (3). Macrophage infiltration is prominent during acute allograft rejection, but few studies have directly examined their role in rejection (3Y5).…”

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confidence: 99%

Macrophages Contribute to Cellular But Not Humoral Mechanisms of Acute Rejection in Rat Renal Allografts

et al. 2013

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The Role of Macrophage Lineage Cells in Kidney Graft Rejection and Survival

Cited by 43 publications

References 116 publications

Increased Circulating T Lymphocytes Expressing HLA-DR in Kidney Transplant Recipients with Microcirculation Inflammation

Increased Circulating T Lymphocytes Expressing HLA-DR in Kidney Transplant Recipients with Microcirculation Inflammation

A Shift towards Pro-Inflammatory CD16+ Monocyte Subsets with Preserved Cytokine Production Potential after Kidney Transplantation

Macrophages Contribute to Cellular But Not Humoral Mechanisms of Acute Rejection in Rat Renal Allografts

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