High proportion of CD95+ and CD38+ in cultured CD8+ T cells predicts acute rejection and infection, respectively, in kidney recipients

Mancebo, Esther; Castro, María José; Allende, Luís M.; Talayero, Paloma; Brunet, Mercè; Millán, Olga; Guirado, L.; López-Hoyos, Marcos; Segundo, David San; Rodrigo, Emilio; Muñoz, Pedro; Boix, Francisco; Viñas, Santiago Llorente; Muro-Amador, Manuel; Paz-Artal, Estela

doi:10.1016/j.trim.2016.01.001

Cited by 13 publications

(16 citation statements)

References 47 publications

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“…[6][7][8] Therefore, it is possible that the dynamics of CD8 + T subsets in the peripheral blood can show a significant change according to "rejection" and "stable" state; hence it has been proposed that monitoring of CD8 + T cells subsets may be useful for detecting acute allograft rejection. [3,9,10] In our previous studies, we investigated the role of CD8 + T cell subsets, especially CCR7 + CD8 + T cells, the naïve T cell, in regard to the suppression of kidney allograft rejection. [11,12] We found that this cell type has a suppressive effect on effector T cell subsets in in vitro study.…”

Section: Introductionmentioning

confidence: 99%

Phenotype and molecular signature of CD8+ T cell subsets in T cell- mediated rejections after kidney transplantation

Seo

Kim

et al. 2020

PLoS ONE

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We investigated the phenotype and molecular signatures of CD8 + T cell subsets in kidneytransplant recipients (KTRs) with biopsy-proven T cell-mediated rejection (TCMR). We included 121 KTRs and divided them into three groups according to the pathologic or clinical diagnosis: Normal biopsy control (NC)(n = 32), TCMR (n = 50), and long-term graft survival (LTGS)(n = 39). We used flowcytometry and microarray to analyze the phenotype and molecular signatures of CD8 + T cell subsets using peripheral blood from those patients and analyzed significant gene expressions according to CD8 + T cell subsets. We investigated whether the analysis of CD8 + T cell subsets is useful for predicting the development of TCMR. CCR7 + CD8 + T cells significantly decreased, but CD28 null CD57 + CD8 + T cells and CCR7-CD45RA + CD8 + T cells showed an increase in the TCMR group compared to other groups (p<0.05 for each); hence CCR7 + CD8 + T cells showed significant negative correlations to both effector CD8 + T cells. We identified genes significantly associated with the change of CCR7 + CD8 + T, CCR7-CD45RA + CD8 + T, and CD28 null CD57 + CD8 + T cells in an ex vivo study and found that most of them were included in the significant genes on in vitro CCR7 + CD8 + T cells. Finally, the decrease of CCR7 + CD8 + T cells relative to CD28 null CD57 + T or CCR7-CD45RA + CD8 + T cells can predict TCMR significantly in the whole clinical cohort. In conclusion, phenotype and molecular signature of CD8 + T subsets showed a significant relationship to the development of TCMR; hence monitoring of CD8 + T cell subsets may be a useful for predicting TCMR in KTRs.

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Section: Introductionmentioning

confidence: 99%

Phenotype and molecular signature of CD8+ T cell subsets in T cell- mediated rejections after kidney transplantation

Seo

Kim

et al. 2020

PLoS ONE

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“…The comparison of predictive performances between our classifier and classifiers in the literature underlines its relevance to pre-kidney transplant risk assessment (Supplemental Table 5). Its accuracy of 82.7% is i) one of the highest among all donor-independent risk assessment models (19,25,30,34,57), ii) comparable to any AR models (19,20,30,34,35,57,58,21,22,(24)(25)(26)(27)(28)(29) and iii) comparable to any SAB data based models for ABMR (22,(24)(25)(26)(27)(28). Furthermore, our classifier is based on SAB, an established diagnostics laboratory tool, thereby facilitating its further use for ACR risk assessment.…”

Section: Discussionmentioning

confidence: 66%

“…For early risk assessment, the large majority of models are donordependent, as they either employ measurements from the early post-transplantation period or utilize donor -derived data (e.g. from crossmatch tests) (19,20,29,30,(21)(22)(23)(24)(25)(26)(27)(28). The most common approach for pre-transplant risk assessment relies on the characterization of HLA antibodies in recipient serum samples by solid phase single HLA antigen bead (SAB) assay (22)(23)(24)(25)(26)(27)31).…”

Section: Introductionmentioning

confidence: 99%

A novel approach reveals that HLA class 1 single antigen bead-signatures provide a means of high-accuracy pre-transplant risk assessment of acute cellular rejection

Wittenbrink

Herrmann

Blázquez-Navarro

et al. 2018

Preprint

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SummaryAcute cellular rejection (ACR) is associated with complications after kidney transplantation, such as graft dysfunction and graft loss. Early risk assessment is therefore critical for the improvement of transplantation outcomes. In this work, we retrospectively analyzed a pre-transplant HLA antigen bead assay data set that was acquired by the e:KID consortium as part of a systems medicine approach. The data set included single antigen bead (SAB) reactivity profiles of 52 low-risk graft recipients (negative complement dependent cytotoxicity crossmatch, PRA<30%) who showed detectable pre-transplant anti-HLA 1 antibodies. To assess whether the reactivity profiles provide a means for ACR risk assessment, we established a novel approach which differs from standard approaches in two aspects: the use of quantitative continuous data and the use of a multiparameter classification method. Remarkably, it achieved significant prediction of the 38 graft recipients who experienced ACR with a balanced accuracy of 82.7% (sensitivity=76.5%, specificity= 88.9%). The resultant classifier achieved one of the highest prediction accuracies in the literature for pre-transplant risk assessment of ACR. Importantly, it can facilitate risk assessment in non-sensitized patients who lack donor-specific antibodies. As the classifier is based on continuous data and includes weak signals, our results emphasize that not only strong but also weak binding interactions of antibodies and HLA 1 antigens contain predictive information.

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“…С другой стороны, учитывая данные о регуляторной активности CD3 + HLA-DR + Т-клеток, механизмы которой опосредованы контактными взаимодействиями между соседними клетками (включая CTLA-4-сигнализацию) [5,13] активацию реактивированных лимфоцитов в отсутствие антигенной стимуляции. В то же время, отсутствие ассоциаций CD4 + CD95 + и CD4 + CD95 + HLA-DR + лимфоцитов с количеством мертвых клеток в культурах TCR-активированных клеток, полученных у больных РА, может свидетельствовать о дефектах апоптоза этой популяции клеток, в частности, опосредованной активацией системы Fas/FasL, что находит подтверждение в литературе [23]. Как уже упоминалось ранее, аутореактивным CD4 + CD45RO + Т-лимфоцитам памяти отводят ключевую роль в патогенезе РА.…”

Section: Discussionunclassified

“…Выявленные нами взаимосвязи между содержанием мертвых клеток и числом CD4 + CD95 + HLA-DR + и CD4 + CD95 + Т-лимфоцитов могут свидетельствовать как об проапоптогенном действии МП на Т-клетки, так и об супрессивных свойствах CD4 + CD95 + HLA-DR + Т-лимфоцитов, ограничивающих чрезмерную активацию CD3 + CD45RO + лимфоцитов у здоровых доноров. Повышение числа CD4 + CD95 + и CD4 + CD95 + HLA-DR + Т-клеток в культурах, полученных от больных РА и инкубированных в присутствии в среде активатора и МП (весь диапазон концентраций), и отсутствие ассоциаций с содержанием мёртвых клеток, может отражать процесс их непрерывной неспецифической активации и/или постоянное присутствие активированных лимфоцитов, вследствие дефектов апоптоза [23].…”

Section: Discussionunclassified

The influence of methylprednisolone on the ability of CD4⁺CD95⁺HLA-DR⁺ T-cells to produce proinflammatory medators in cultures of TCR-activated CD3⁺CD45RO⁺ T-lymphocytes from patients with rheumatoid arthritis

et al. 2017

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The effect of different concentrations of the glucocorticoid (GC) methylprednisolone (MP) on CD4+CD95+HLA-DR+ T-cells and their ability to produce proinflammatory mediators in cultures of TCR-stimulated CD3+CD45RO+ T-lymphocytes in the in vitro system was investigated. T cells were obtained from healthy donors and patients with rheumatoid arthritis (RA).Under conditions of TCR-activation, MP increased the number of CD4+HLA-DR+CD95+ cells in CD3+CD45RO+ cultures obtained from RA patients and did not change their content in the control group. In general, MP decreased production of proinflammatory factors (IFN-, IL-2, IL-17, IL-21 and TNF-) by TCR-activated CD3+CD45RO+ cells from healthy donors and RA, consistent with the overall immunosuppressive mechanism of GC action. The correlation between CD4+CD45RO+HLA-DR+CD95+ T-cell contents and parameters reflecting production of proinflammatory mediators (IL-17, IL-21 and TNF-) in RA patients indicates maintenance of the pro-inflammatory potential of this T-cell population exposed to GC action. We suggest that relative resistance of CD4+CD45RO+CD95+HLA-DR+ T-cells of RA patients to the suppressor effect of GC leads to maintenance and even enhancement in the functional capacities of autoreactive cells in the pathogenesis of RA.

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High proportion of CD95+ and CD38+ in cultured CD8+ T cells predicts acute rejection and infection, respectively, in kidney recipients

Cited by 13 publications

References 47 publications

Phenotype and molecular signature of CD8+ T cell subsets in T cell- mediated rejections after kidney transplantation

Phenotype and molecular signature of CD8+ T cell subsets in T cell- mediated rejections after kidney transplantation

A novel approach reveals that HLA class 1 single antigen bead-signatures provide a means of high-accuracy pre-transplant risk assessment of acute cellular rejection

The influence of methylprednisolone on the ability of CD4⁺CD95⁺HLA-DR⁺ T-cells to produce proinflammatory medators in cultures of TCR-activated CD3⁺CD45RO⁺ T-lymphocytes from patients with rheumatoid arthritis

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High proportion of CD95+ and CD38+ in cultured CD8+ T cells predicts acute rejection and infection, respectively, in kidney recipients

Cited by 13 publications

References 47 publications

Phenotype and molecular signature of CD8+ T cell subsets in T cell- mediated rejections after kidney transplantation

Phenotype and molecular signature of CD8+ T cell subsets in T cell- mediated rejections after kidney transplantation

A novel approach reveals that HLA class 1 single antigen bead-signatures provide a means of high-accuracy pre-transplant risk assessment of acute cellular rejection

The influence of methylprednisolone on the ability of CD4+CD95+HLA-DR+ T-cells to produce proinflammatory medators in cultures of TCR-activated CD3+CD45RO+ T-lymphocytes from patients with rheumatoid arthritis

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The influence of methylprednisolone on the ability of CD4⁺CD95⁺HLA-DR⁺ T-cells to produce proinflammatory medators in cultures of TCR-activated CD3⁺CD45RO⁺ T-lymphocytes from patients with rheumatoid arthritis