Changes in the number of circulating TCM and TEM subsets in renal transplantation: relationship with acute rejection and induction therapy

Abstract

Effector (TEM) and central memory (TCM) T cells have been recently described as the main memory T-cell subsets generated after primary immune response, with a potential role in graft rejection after rechallenge with alloantigen. Because of their effector function, they could be involved in driving the response against the allograft, leading to rejection. In this study, we sought to investigate the different memory T-cell subpopulations in peripheral blood from a cohort of 90 patients who underwent consecutive renal transplant, and their association with acute rejection (AR) episodes and induction therapy. Twenty-one of them were monitored in the short term during the first 2 months after transplantation. Three of them suffered an AR but no changes in the circulating levels of either CD4+ or CD8+ TEM were observed as compared with rejection-free renal transplant patients. In total, 69 patients out of 90 were monitored in the long term. Even 2 years after transplantation, maintained increased numbers of peripheral blood CD4+ TEM were observed in patients suffering with AR. Interestingly, induction therapy with thymoglobulin, but not with basiliximab, produced an increase in circulating CD4+ TEM cells at 6 months after transplantation. In conclusion, our data suggest that AR episodes favor the induction of TEM cells in the periphery of renal transplant patients in the long term. It remains to be determined whether such an effect has any impact on long-term renal transplantation.

The Magnitude and Functionality of SARS-CoV-2 Reactive Cellular and Humoral Immunity in Transplant Population Is Similar to the General Population Despite Immunosuppression

“… 30 This was associated with a higher immunologic age defined as the ratio of memory cells among total CD4 + T cells of the more severely affected patients. 30 Therefore, the higher immunologic age of Tx patients observed in our and previous cohorts, 31 - 34 might convey a higher risk of critical COVID-19 as recently hypothesized by Bacher et al 30 …”

“…Chronic organ failure and transplantation result in an aged immune system with a reduced repertoire of naive T cells and possible dependence on crossreactive memory T cell responses to new immunologic challenges. 32 - 34 , 39 Interestingly, a recent study described a lower functional avidity and higher polyclonality of SARS-CoV-2–reactive T cells in hospitalized as compared to nonhospitalized patients, despite higher frequencies of SARS-CoV-2–reactive T cells. 30 This was associated with a higher immunologic age defined as the ratio of memory cells among total CD4 + T cells of the more severely affected patients.…”

Donor-specific hypo-responsiveness occurs in simultaneous liver-kidney transplant recipients after the first year

“…12 In fact, both the effector and central memory T cells recover to their pretransplantation levels as early as 3 months after kidney transplantation in patients who receive thymoglobulin induction. 11 At 6 months, the frequency of effector memory T cells have been shown to be similar in patients regardless of thymoglobulin induction 13 and similar to pretransplantation numbers. 14 In the current study, the overall frequency of different immunophenotypes among the KTA recipients was not different between those who had and those who had not received T-cell depleting induction.…”

Molecular Diversity of Clinically Stable Human Kidney Allografts

“… 68 In the hSTA/mAR grafts, these cells are primed to differentiate into Tem with low levels of antigen recognition, such as with varying exposure to baseline immunosuppression. 69 Hence, identification of the hSTA/mAR phenotype in an otherwise clinically and histologically stable allograft may be of critical importance to triage allografts at greater risk of accelerated temporal immune injury.…”