Induction of Accommodation by Anti-complement Component 5 Antibody-based Immunosuppression in ABO-incompatible Heart Transplantation.

Background: Plasmapheresis in combination with immunoglobulin and rituximab is often used to induce accommodation in ABO-incompatible (ABOi) living-donor transplantation; however, this regimen cannot be applied to cases of ABOi deceased-donor transplantation. Here, we investigated whether an anti-complement component 5 (C5) antibody-based regimen can induce accommodation in ABOi heart transplantation.

Methods: Both IgM and IgG anti-blood type A antibodies were induced in wild-type mice by sensitization using human blood type A antigen.

Peripheral blood transcriptome analysis and development of classification model for diagnosing antibody-mediated rejection vs accommodation in ABO-incompatible kidney transplant.

The major obstacle to successful ABO blood group-incompatible kidney transplantation (ABOi KT) is antibody-mediated rejection (AMR). This study aimed to investigate transcriptional profiles through RNA sequencing and develop a minimally invasive diagnostic tool for discrimination between accommodation and early acute AMR in ABOi KT. Twenty-eight ABOi KT patients were selected: 18 with accommodation and 10 with acute AMR at the 10th day posttransplant protocol biopsy.

Anti-CD45RB Antibody Therapy Attenuates Renal Ischemia-Reperfusion Injury by Inducing Regulatory B Cells.

Background: Regulatory B cells are a newly discovered B cell subset that suppresses immune responses. Recent studies found that both anti-CD45RB and anti-Tim-1 treatments regulate immune responses by inducing regulatory B cells; however, the role of these cells in renal ischemia-reperfusion injury (IRI) is unknown.

Methods: Using mouse models, including T cell-deficient (RAG1 knockout and TCR knockout) mice and B cell-deficient (MT) mice, we investigated the effects of regulatory B cells and anti-CD45RB on IRI and the mechanisms underlying these effects.

Identification of Human B-1 Helper T Cells With a Th1-Like Memory Phenotype and High Integrin CD49d Expression.

Human B-1 cells have been proposed to be CD20CD27CD43CD1c B cells found in the umbilical cord and adult peripheral blood, but their regulatory mechanisms have not been well elucidated. Previously, we reported that mouse CD49d CD4 T cells could enhance the secretion of natural antibodies by B-1 cells. In this study, we aimed to investigate the presence and helper functions of the human equivalents of murine CD49d CD4 T cells.

VDJ gene usage among B-cell receptors in ABO-incompatible kidney transplantation determined by RNA-seq Transcriptomic analysis.

Background: Studies on B-cell subtypes and V(D)J gene usage of B-cell receptors in kidney transplants are scarce. This study aimed to investigate V(D)J gene segment usage in ABO-incompatible (ABOi) kidney transplant (KT) patients compared to that in ABO-compatible (ABOc) KT patients.

Methods: We selected 16 ABOi KT patients with accommodation (ABOiA), 6 ABOc stable KT patients (ABOcS), and 6 ABOi KT patients with biopsy-proven acute antibody-mediated rejection (ABOiR) at day 10, whose graft tissue samples had been stored in the biorepository between 2010 and 2014.

Role of Human CD200 Overexpression in Pig-to-Human Xenogeneic Immune Response Compared With Human CD47 Overexpression.

Background: Macrophages play important roles in xenograft rejection. Here, we investigated whether overexpression of human CD200 or CD47 in porcine endothelial cells (PEC) can suppress macrophages activation in xenogeneic immune responses.

Methods: PECs and human macrophages were incubated together, harvested, and analyzed for in vitro macrophage phagocytic and cytotoxicity activity, and cytokine release.

The P2X7 receptor antagonist, oxidized adenosine triphosphate, ameliorates renal ischemia-reperfusion injury by expansion of regulatory T cells.

Extracellular adenosine triphosphate (ATP) binds to purinergic receptors and, as a danger molecule, promotes inflammatory responses. Here we tested whether periodate-oxidized ATP (oATP), a P2X7 receptor (P2X7R) antagonist can attenuate renal ischemia-reperfusion injury and clarify the related cellular mechanisms. Treatment with oATP prior to ischemia-reperfusion injury decreased blood urea nitrogen, serum creatinine, the tubular injury score, and tubular epithelial cell apoptosis after injury.

IL-2/anti-IL-2 complexes ameliorate lupus nephritis by expansion of CD4CD25Foxp3 regulatory T cells.

Adoptive transfer of regulatory T cells (Tregs) can delay disease progression and reduce mortality in lupus-prone mice. Here, we tested whether complex (IL-2C) consisting of IL-2 and anti-IL-2 monoclonal antibody (JES6-1) ameliorates lupus nephritis by expanding Tregs as an alternative to problematic Treg infusion therapy. IL-2C treatment of NZB/W F1 mice induced an effective and sustained expansion of CD4CD25Foxp3 Tregs in both the kidneys and spleen along with decreased renal infiltration of T cells, B cells, and innate immune cells.

Granulocyte colony-stimulating factor treatment ameliorates lupus nephritis through the expansion of regulatory T cells.

Background: Granulocyte colony-stimulating factor (G-CSF) can induce regulatory T cells (Tregs) as well as myeloid-derived suppressor cells (MDSCs). Despite the immune modulatory effects of G-CSF, results of G-CSF treatment in systemic lupus erythematosus are still controversial. We therefore investigated whether G-CSF can ameliorate lupus nephritis and studied the underlying mechanisms.

Beneficial effects of the transgenic expression of human sTNF-αR-Fc and HO-1 on pig-to-mouse islet xenograft survival.

Both human soluble tumor necrosis factor-α receptor-Fc (sTNF-αR-Fc) and heme oxygenase-1 (HO-1) transgenic pigs have been generated previously for xenotransplantation. Here, we investigated whether overexpression of sTNF-αR-Fc or HO-1 in pig islets prolongs islet xenograft survival. Adult porcine islets were isolated from human sTNF-αR-Fc or HO-1 transgenic and wild type pigs, and were transplanted into diabetic nude mice.

Effects of stimulating interleukin -2/anti- interleukin -2 antibody complexes on renal cell carcinoma.

Background: Current therapies for advanced renal cell carcinoma (RCC) have low cure rates or significant side effects. It has been reported that complexes composed of interleukin (IL)-2 and stimulating anti-IL-2 antibody (IL-2C) suppress malignant melanoma growth. We investigated whether it could have similar effects on RCC.

Early Development in the Peritoneal Cavity of CD49dhigh Th1 Memory Phenotype CD4+ T Cells with Enhanced B Cell Helper Activity.

The Th cells that regulate peritoneal B-1 cell functions have not yet been well characterized. To address this question, we investigated peritoneal CD4(+) T cells, observed a high frequency of the conjugates of B-CD4(+) T cells in the peritoneal cavity, and identified a population of CD49d(high)CD4(+) T cells that constituted about half of all CD4(+) T cells in the peritoneal cavity, but were rarely found in other compartments. Peritoneal CD49d(high)CD4(+) T cells were CD44(high)CD62L(low); expressed integrin α4β1 and CXCR3; and rapidly secreted IFN-γ, TNF-α, and IL-2, showing features of proinflammatory Th1 cells.

Reversible expression of CD138 on mature follicular B cells is downregulated by IL-4.

CD138, known as a marker of plasma cells, was reported to be expressed to an intermediate level in the murine bone marrow precursor B cells. Here an intermediate level of CD138 expression was also noted in a subpopulation of splenic follicular B cells, which were distinguishable from CD138(high) plasma cells, whereas the majority of transitional or marginal zone B cells did not express CD138. These CD138(int) B cells were IgM(low)IgD(high) mature B cells, located within follicular B cell zone, and expressed a lower level of CD21 than CD138(-) follicular B cells.

LPS-induced migration of peritoneal B-1 cells is associated with upregulation of CXCR4 and increased migratory sensitivity to CXCL12.

B-1 cells, which constitute a predominant lymphocyte subset in serosal cavities and produce most of natural antibodies, are subdivided into the CD5(+) B-1a and CD5(-) B-1b cell subpopulations, but the differential roles of B-1a and B-1b cells are not well understood. We report that B-1a cells preferentially migrate out of the peritoneal cavity and upregulate the expression of CXCR4 with heightened sensitivity to CXCL12 and CXCL13 upon LPS treatment compared to B-1b and B-2 cells. Whereas B-1a cells were slightly more abundant than B-1b and B-2 cells in the homeostatic condition, the number of B-1a cells preferentially decreased 48 hr after LPS treatment.