Basiliximab impairs regulatory T cell (TREG) function and could affect the short-term graft acceptance in children with heart transplantation

López‐Abente, Jacobo; Martínez‐Bonet, Marta; Bernaldo‐de‐Quirós, Esther; Camino, Manuela; Gil, Nuria; Panadero, Esther; Gil-Jaurena, Juan-Miguel; Clemente, Maribel; Urschel, Simon; West, Lori J.; Pion, Marjorie; Correa‐Rocha, Rafael

doi:10.1038/s41598-020-80567-9

Cited by 22 publications

(25 citation statements)

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“…Poor CD4 + CD25 + T cell reconstitution increased the risk of infections (51). We observed that patients who recovered from SR-aGVHD after basiliximab treatment had a slower CD4 + CD25 + T-cell recovery compared with event-free HID HSCT recipients, which was supported by previous studies (52,53). Chakupurakal et al (53) observed significant depletion of CD4 + CD25 + T cells in SR-aGVHD patients treated with basiliximab, and Vondran et al (54) reported that basiliximab downregulated the expression of CD25 on T cells in vitro.…”

Section: Discussionsupporting

confidence: 85%

Immune Reconstitution of Patients Who Recovered From Steroid-Refractory Acute Graft-Versus-Host Disease After Basiliximab Treatment

et al. 2022

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We aimed to identify the characteristics of immune reconstitution (IR) in patients who recovered from steroid-refractory acute graft-versus-host disease (SR-aGVHD) after basiliximab treatment. A total of 179, 124, 80, and 92 patients were included in the analysis for IR at 3, 6, 9, and 12 months, respectively, after haploidentical donor hematopoietic stem cell transplantation (HID HSCT). We observed that IR was fastest for monocytes and CD8+ T cells, followed by lymphocytes, CD3+ T cells, and CD19+ B cells and slowest for CD4+ T cells. Almost all immune cell subsets recovered comparably between patients receiving <5 doses and ≥5 doses of basiliximab. Most immune cell subsets recovered comparably between SR-aGVHD patients who recovered after basiliximab treatment and event-free HID HSCT recipients. Patients who recovered from SR-aGVHD after basiliximab treatment experienced satisfactory IR, which suggested that basiliximab may not have prolonged the negative impact on IR in these patients.

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Section: Discussionsupporting

confidence: 85%

Immune Reconstitution of Patients Who Recovered From Steroid-Refractory Acute Graft-Versus-Host Disease After Basiliximab Treatment

et al. 2022

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“…Values and functional markers (CD39, CTLA4, Ki67, and HLA-DR) of Foxp3+ Treg cells (CD3+CD4+CD25+Foxp3+) and frequency of Foxp3+ Treg "recent thymic emigrants" (RTE) (CD45RA+CD31+) were also analyzed in PBMCs by intracellular staining as previously described. 12,13 Gating strategies for all these immune populations and subpopulations are shown in Figure 2.…”

Section: Sample Processing and Immune Monitoringmentioning

confidence: 99%

The Presence of a Marked Imbalance Between Regulatory T Cells and Effector T Cells Reveals That Tolerance Mechanisms Could Be Compromised in Heart Transplant Children

Bernaldo‐de‐Quirós

López‐Abente

Camino

et al. 2021

Transplantation Direct

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Pediatric TransplantationBackground. Regulatory T cells (Treg) are crucial for the induction and maintenance of graft tolerance. In pediatric heart transplant procedures, the thymus is routinely excised, removing the primary source of T-cell replenishment. Consequently, thymectomy joined to the effects of immunosuppression on the T-cell compartment may have a detrimental impact on Treg values, compromising the intrinsic tolerance mechanisms and the protective role of Treg preventing graft rejection in heart transplant children. Methods. A prospective study including 7 heart transplant children was performed, and immune cell populations were evaluated periodically in fresh peripheral blood at different time points before and up to 3 y posttransplant. Results. Treg counts decreased significantly from the seventh-month posttransplant. Furthermore, there was a significant increase in effector memory and terminally differentiated effector memory T cells coinciding with the fall of Treg counts. The Treg/Teffector ratio, a valuable marker of the tolerance/rejection balance, reached values around 90% lower than pretransplant values. Additionally, a negative correlation between Treg count and T effector frequency was observed. Particularly, when Treg count decreases below 50 or 75 cells/μL in the patients, the increase in the frequency of T effector CD4+ and CD8+, respectively, experiences a tipping point, and the proportion of T-effector cells increases dramatically.Conclusions. These results reveal that interventions employed in pediatric heart transplantation (immunosuppression and thymectomy) could induce, as an inevitable consequence, a dysregulation in the immunologic status characterized by a marked imbalance between Treg and T effector, which could jeopardize the preservation of tolerance during the period with the higher incidence of acute rejection.

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“…Induction agents can affect T cells, including Tregs, at least transiently. Alemtuzumab and thymoglobulin can lead to an increased ratio of Tregs to effector T cells while basiliximab and daclizumab may decrease that ratio 52–56 …”

Section: Discussionmentioning

confidence: 99%

“…Given the small sample size, it was not possible to adjust for daclizumab may decrease that ratio. [52][53][54][55][56] The duration of the impact of induction agents on Tregs is not known, but if it is long lasting, then type of induction may have confounded the relation between sex and Tregs in our study. Even beginning to determine how to quantify adherence as a possible confounder in the relationship between age or sex and immune profile is challenging.…”

Section: (D)mentioning

confidence: 95%

Age‐ and sex‐mediated differences in T lymphocyte populations of kidney transplant recipients

Dziarmaga

Sapir‐Pichhadze

et al. 2021

Pediatric Transplantation

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Background: Graft failure rates increase through childhood and adolescence, decline in adulthood, and are higher in female than male kidney transplant recipients (KTR) until middle age. We aimed to describe age-and sex-related differences in T-cell subsets among KTR to determine which differences may help to explain the differences in kidney graft failure rates. Methods: Effector T (Teff)-cell and regulatory T (Treg)-cell phenotypes in PBMCsfrom healthy controls and KTR, who were at least 1 year post-transplant with stable graft function under immunosuppression, were analyzed by flow cytometry. The effects of age, sex, and status (KTR or control) were analyzed using linear regressions. Results:We enrolled 20 male and 21 female KTR and 20 male and 20 female controls between 3 and 29 years of age. CD3+ T-cell frequencies were not associated with age or sex but were higher in KTR than controls. There were no differences in CD4+ and CD8+ frequencies. Th1 (IFNγ+ IL-4− IL-17A−) and Th17 (IL-17A+) frequencies within the CD4+ T-cell population were higher at older ages. The frequencies of FOXP3 + Helios + Treg cells in CD4+ CD25+ CD127− T cells were lower in females than males and in KTR than controls.Conclusions: Increasing frequencies of Th1 and Th17 cells with increasing age mirrors the increasing graft failure rates from childhood to young adulthood. Importantly, sex differences in frequencies of circulating Treg cells may suggest a role in the sex differences in graft failure rates.

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Basiliximab impairs regulatory T cell (TREG) function and could affect the short-term graft acceptance in children with heart transplantation

Cited by 22 publications

References 49 publications

Immune Reconstitution of Patients Who Recovered From Steroid-Refractory Acute Graft-Versus-Host Disease After Basiliximab Treatment

Immune Reconstitution of Patients Who Recovered From Steroid-Refractory Acute Graft-Versus-Host Disease After Basiliximab Treatment

The Presence of a Marked Imbalance Between Regulatory T Cells and Effector T Cells Reveals That Tolerance Mechanisms Could Be Compromised in Heart Transplant Children

Age‐ and sex‐mediated differences in T lymphocyte populations of kidney transplant recipients

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