Differential Effects of B and T Lymphocyte Attenuator and Programmed Death-1 on Acceptance of Partially versus Fully MHC-Mismatched Cardiac Allografts

Abstract

Objective To conduct a systematic review and metaanalysis of the evidence on the effects of β-alanine supplementation on exercise capacity and performance. Design This study was designed in accordance with PRISMA guidelines. A 3-level mixed effects model was employed to model effect sizes and account for dependencies within data. Data sources 3 databases (PubMed, Google Scholar, Web of Science) were searched using a number of terms ('β-alanine' and 'Beta-alanine' combined with 'supplementation', 'exercise', 'training', 'athlete', 'performance' and 'carnosine'). Eligibility criteria for selecting studies Inclusion/ exclusion criteria limited articles to double-blinded, placebo-controlled studies investigating the effects of β-alanine supplementation on an exercise measure. All healthy participant populations were considered, while supplementation protocols were restricted to chronic ingestion. Cross-over designs were excluded due to the long washout period for skeletal muscle carnosine following supplementation. A single outcome measure was extracted for each exercise protocol and converted to effect sizes for meta-analyses. Results 40 individual studies employing 65 different exercise protocols and totalling 70 exercise measures in 1461 participants were included in the analyses. A significant overall effect size of 0.18 (95% CI 0.08 to 0.28) was shown. Meta-regression demonstrated that exercise duration significantly ( p=0.004) moderated effect sizes. Subgroup analyses also identified the type of exercise as a significant ( p=0.013) moderator of effect sizes within an exercise time frame of 0.5-10 min with greater effect sizes for exercise capacity (0.4998 (95% CI 0.246 to 0.753)) versus performance (0.1078 (95% CI −0.201 to 0.416)). There was no moderating effect of training status ( p=0.559), intermittent or continuous exercise ( p=0.436) or total amount of β-alanine ingested ( p=0.438). Co-supplementation with sodium bicarbonate resulted in the largest effect size when compared with placebo (0.43 (95% CI 0.22 to 0.64)). Summary/conclusions β-alanine had a significant overall effect while subgroup analyses revealed a number of modifying factors. These data allow individuals to make informed decisions as to the likelihood of an ergogenic effect with β-alanine supplementation based on their chosen exercise modality.

The TNF receptor and Ig superfamily members form an integrated signaling circuit controlling dendritic cell homeostasis

“…So far, the functional role of BTLA has mainly been viewed from the perspective of T cells, where signaling induces a key coinhibitory signal attenuating host T cell responses. For example, HVEM-BTLA pathway regulates acceptance of partially MHC-mismatched cardiac allograft [58]. BTLA expression was also found to be highly induced on anergic CD4+ T cells [59].…”

Programmed cell death 1 (PD‐1) and its ligand PD‐L1 are required for allograft tolerance

“…Similarly, injection of mAb to PD-1 [13] or PD-L1 [14] accelerated allograft rejection in immunosup-pressed recipients. However, although most studies indicate that the PD-1/PD-L1 pathway negatively regulates T cell activation and proliferation, there is evidence for a positive costimulatory effect of PD-L1 on TCR activation of naive murine T cells [3,15].…”

B and T Lymphocyte Attenuator Regulates B Cell Receptor Signaling by Targeting Syk and BLNK

“…However, these mice display hyperproliferative T and B cell responses to TCR-and BCR-mediated activation, respectively (9, 11). Furthermore, loss of BTLA function leads to increased susceptibility to experimental autoimmune encephalomyelitis and MHC-mismatched allograft rejection, supporting the role of BTLA in modulating T cell activation and effector responses (11,12).Surface expression analysis of BTLA indicates that it is expressed on a wide number of lymphocytes in mice. It is most highly expressed on B cells, followed by CD4 ϩ T cells, and lower expression on CD8 ϩ T cells, macrophages, dendritic cells, and NK cells (9, 13).…”

“…However, these mice display hyperproliferative T and B cell responses to TCR-and BCR-mediated activation, respectively (9,11). Furthermore, loss of BTLA function leads to increased susceptibility to experimental autoimmune encephalomyelitis and MHC-mismatched allograft rejection, supporting the role of BTLA in modulating T cell activation and effector responses (11,12).…”