Aging and End Stage Renal Disease Cause A Decrease in Absolute Circulating Lymphocyte Counts with A Shift to A Memory Profile and Diverge in Treg Population

Abstract

There is a growing number of elderly kidney transplant (Ktx) recipients. Elderly recipients present lower acute rejection rates but higher incidence of infection and malignancies. Aging per se seems to result in a shift to memory profile and chronic kidney disease (CKD) in premature immunological aging. Understanding aging and CKD effects on the immune system can improve elderly Ktx immunosuppression. We analyzed the effects of aging and CKD in the immune system, comparing healthy adults (HAd) (n=14, 26±2y), healthy elderly (HEld) (n=15, 79±7y), end stage renal disease (ESRD) adults (EnAd) (n=18, 36±7y) and ESRD elderly (EnEld) (n=31, 65±3y) prior to Ktx regarding their naïve, memory and regulatory T and B peripheral lymphocytes. Aging and ESRD presented additive effect decreasing absolute numbers of B and T-lymphocytes, affecting memory, naive and regulatory subsets without synergic effect. Both resulted in higher percentages of T memory subsets and opposing effects on regulatory T (TREG) subsets, higher percentage in aging and lower in ESRD. Combined effect of aging and ESRD also resulted in higher regulatory B cell percentages. In addition to global lymphopenia and TCD4+ memory shift in both aging and ESRD, aging shifts to an immunoregulatory profile, inducing a increase in TREG percentages, contrasting with ESRD that decreases TREGs. Differential immunosuppression regimens for elderly Ktx may be required. (ClinicalTrials.gov number: NTC01631058).

Compromised steady‐state germinal center activity with age in nonhuman primates

“…A significant decrease of the absolute numbers of circulating lymphocytes was found in old NHPs at the steady‐state (absence of recent/current infection or vaccination) mainly affected by the selective drop of CD4 T‐cell counts. In line with previous human studies (Freitas et al, ), we found a shift from naïve to memory status for both CD4 and CD8 T cells in aged animals, a change more evident in blood compared to LNs. This shift was associated with an increase of the circulating “effector memory” compartment of both CD4 and CD8 T cells.…”

“…Taken together, the models and data indicate that the mutual regulation between GC B cells and other GC immune cell populations may differ with respect to aging. (Freitas et al, 2019), we found a shift from naïve to memory status for both CD4 and CD8 T cells in aged animals, a change more evident in blood compared to LNs. This shift was associated with an increase of the circulating "effector memory" compartment of both CD4 and CD8 T cells.…”

“…Similarly to TCR, the BCR repertoire in humans has been shown to decline with age and becomes dysfunctional (de Bourcy et al, ; Boyd, Liu, Wang, Martin, & Dunn‐Walters, ; Dunn‐Walters, ; Wang et al, ). A shift in T‐cell and B‐cell subtypes from naïve to memory, a significant increase in circulating regulatory CD4 T cells (Tregs) (Freitas et al, ), and changes in T‐cell and B‐cell signaling have been described in elderly individuals (Beatriz Suarez‐Alvarez, ; Le Page, Dupuis, Larbi, Mitwowski, & Fulop, ; Naylor et al, ). Furthermore, aging in humans is associated with increased circulating pro‐inflammatory mediators (Franceschi et al, ; Metcalf et al, ).…”

“…-Walters, 2013;Dunn-Walters, 2016;Wang et al, 2014). A shift in T-cell and B-cell subtypes from naïve to memory, a significant increase in circulating regulatory CD4 T cells (Tregs) (Freitas et al, 2019), and changes in T-cell and B-cell signaling have been described in elderly individuals (Beatriz Suarez-Alvarez, 2017;…”

COVID-19 Pneumonia in a Hemodialysis Patient

“…Because hemodialysis patients have disorders of B-cell and T-cell function [7,8], patients may have atypical presentations. Lymphopenia is common in patients with COVID-19 and might be a critical factor associated with disease severity and mortality in general patients [9].…”