A New Window into the Human Alloresponse

DeWolf, Susan; Shen, Yufeng; Sykes, Megan

doi:10.1097/tp.0000000000001064

Cited by 23 publications

(20 citation statements)

References 143 publications

(130 reference statements)

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“…This might be an explanation for the trend in higher frequencies of proliferating T cells, as well as precursor frequencies comparing CMV seropositive responders to CMV impacts T cells in elderly ESRD patients V C 2016 British Society for Immunology, Clinical and Experimental Immunology, 186: 239-248 their negative counterparts (Supporting information, Table S2). By using high-throughput sequencing of the diversity of the TCR repertoire [40,58] this might provide a more supportive functional read-out.…”

Section: Discussionmentioning

confidence: 99%

Latency for cytomegalovirus impacts T cell ageing significantly in elderly end-stage renal disease patients

Huang¹,

Langerak

Baan³

et al. 2016

Clinical and Experimental Immunology

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The number of elderly patients with end-stage renal disease (ESRD) has increased significantly during the last decade. Elderly ESRD patients are vulnerable to infectious complications because of an aged immune system. Additional immunological ageing effects may be derived from the uraemic environment and cytomegalovirus (CMV) latency. Elderly patients may be affected by these factors in particular, but data in this age group are limited. To assess the degree of immunological ageing and proliferative capacity of T lymphocytes, 49 elderly ESRD patients (defined as aged ≥ 65 years) on the renal transplantation waiting list were recruited and compared to 44 elderly healthy individuals (HI), matched for age and CMV serostatus. CMV latency was associated with more highly differentiated CD4 and CD8 T cells in both elderly HI and patients. Elderly CMV seropositive ESRD patients showed a substantial reduction in the number of naive CD4 and CD8 T cells compared with age- and CMV serostatus-matched HI. Elderly ESRD patients also showed significantly decreased numbers of central memory CD4 and CD8 T cells compared with HI, independently of CMV serostatus. In addition, thymic output and relative telomere length of both CD4 and CD8 T cells were decreased in CMV seropositive ESRD patients compared with HI. The proliferative capacity of T cells was similar for patients and HI. Elderly ESRD patients have an advanced aged T cell compartment when compared to age-matched healthy controls, which is driven mainly by CMV latency.

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Section: Discussionmentioning

confidence: 99%

Latency for cytomegalovirus impacts T cell ageing significantly in elderly end-stage renal disease patients

Huang¹,

Langerak

Baan³

et al. 2016

Clinical and Experimental Immunology

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“…Also, the lack of reliable biomarkers to identify donor-specific tolerance is a hurdle to structured immunosuppression tapering in clinical transplantation [4, 5]. However, recent advances in identifying biomarkers of transplant tolerance [4, 6] and especially in measuring and tracking the recipient anti-donor alloreactive repertoire [6–8] are likely to facilitate such efforts in the future.…”

Section: Challenges In Translating Transplantation Tolerance To the Cmentioning

confidence: 99%

“…However, recent advances in identifying biomarkers of transplant tolerance [4, 6] and especially in measuring and tracking the recipient anti-donor alloreactive repertoire [6–8] are likely to facilitate such efforts in the future.…”

Section: Challenges In Translating Transplantation Tolerance To the Cmentioning

confidence: 99%

Mechanisms of Mixed Chimerism-Based Transplant Tolerance

Zuber

Sykes

2017

Trends in Immunology

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Immune responses to allografts represent a major barrier in organ transplantation. Immune tolerance to avoid chronic immunosuppression is a critical goal in the field, recently achieved in the clinic by combining bone marrow transplantation with kidney transplantation following non-myeloablative conditioning. At high levels of chimerism, such protocols can permit central deletional tolerance, yet with a significant risk of graft-versus-host disease (GVHD). In contrast, transient chimerism-based tolerance is devoid of GVHD risk and appears to initially depend on regulatory T cells followed by a gradual, presumably peripheral, clonal deletion of donor-reactive T cells. Here, we review recent mechanistic insights into tolerance and the development of more robust and safer protocols for tolerance induction that will be guided by innovative immune monitoring tools.

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“…The early studies that led to these widely quoted values along with many other observations about the alloresponse, however, were performed a decade or more ago (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12). Furthermore, most studies investigating the T cell alloresponse have been in mice, given the need for transgenic tools and other techniques not feasible in humans (13).…”

Section: Introductionmentioning

confidence: 99%