Germinal Center B Cells are Uniquely Targeted by Antibody-Suppressor CXCR5CD8 T Cells.

Background: Alloprimed antibody-suppressor CXCR5CD8 T cells (CD8 T cells) downregulate alloantibody production, mediate cytotoxicity of IgG B cells, and prolong allograft survival. The purpose of this investigation was to determine which immune-cell subsets are susceptible to CD8 T cell-mediated cytotoxicity or noncytotoxic suppression.

Methods: Alloprimed immune-cell subsets were evaluated for susceptibility to CD8 T cell-mediated in vitro cytotoxicity and/or suppression of intracellular cytokine expression.

Antibody-Suppressor CXCR5+CD8+ T Cells Are More Potent Regulators of Humoral Alloimmunity after Kidney Transplant in Mice Compared to CD4+ Regulatory T Cells.

Adoptive cell therapy (ACT), especially with CD4+ regulatory T cells (CD4+ Tregs), is an emerging therapeutic strategy to minimize immunosuppression and promote long-term allograft acceptance, although much research remains to realize its potential. In this study, we investigated the potency of novel Ab-suppressor CXCR5+CD8+ T cells (CD8+ TAb-supp) in comparison with conventional CD25highFoxp3+CD4+ Tregs for suppression of humoral alloimmunity in a murine kidney transplant (KTx) model of Ab-mediated rejection (AMR). We examined quantity of peripheral blood, splenic and graft-infiltrating CD8+ TAb-supp, and CD4+ Tregs in KTx recipients and found that high alloantibody-producing CCR5 knockout KTx recipients have significantly fewer post-transplant peripheral blood and splenic CD8+ TAb-supp, as well as fewer splenic and graft-infiltrating CD4+ Tregs compared with wild-type KTx recipients.

CXCR5 + CD8 + T Cell-mediated Suppression of Humoral Alloimmunity and AMR in Mice Is Optimized With mTOR and Impaired With Calcineurin Inhibition.

Background: Adoptive cellular therapy (ACT) with antibody-suppressor CXCR5 + CD8 + T cells (CD8 + T Ab-supp ) inhibits alloantibody production, antibody-mediated rejection (AMR), and prolongs graft survival in multiple transplant mouse models. However, it is not known how conventional immunosuppressive agents impact the efficacy of CD8 + T Ab-supp ACT.

Methods: We investigated the efficacy of CD8 + T Ab-supp cell ACT when combined with calcineurin inhibitor (CNi) or mammalian target of rapamycin inhibitor (mTORi) in a murine model of kidney transplant.

Spinal Stroke following Kidney Transplant.

Complications are a part of surgery. Spinal infarctions are a dreaded complication of aortic surgery. We present a patient who developed a spinal infarct after a kidney transplant.

Thoracic transplantation during the COVID-19 pandemic.

The worldwide pandemic caused by COVID-19, resulting from the infection by betacoronarvirus SARS-CoV-2, has dramatically altered healthcare worldwide. Due to the highly contagious nature of SARS-CoV2, coupled with hospitals and intensive care units being overwhelmed, numerous transplant programs either slowed or shut down completely. While there have been isolated reports of COVID-19 in transplant recipients, no study to date has examined how COVID-19 affected actual transplant patterns and outcomes in the United States.

Invariant NKT Cells Promote the Development of Highly Cytotoxic Multipotent CXCR3CCR4CD8 T Cells That Mediate Rapid Hepatocyte Allograft Rejection.

Hepatocyte transplant represents a treatment for metabolic disorders but is limited by immunogenicity. Our prior work identified the critical role of CD8 T cells, with or without CD4 T cell help, in mediating hepatocyte rejection. In this study, we evaluated the influence of invariant NKT (iNKT) cells, uniquely abundant in the liver, upon CD8-mediated immune responses in the presence and absence of CD4 T cells.

CXCR5CD8 T cells: A Review of their Antibody Regulatory Functions and Clinical Correlations.

CD8 T cells have conventionally been studied in relationship to pathogen or tumor clearance. Recent reports have identified novel functions of CXCR5CD8 T cells that can home to lymphoid follicles, a key site of antibody production. In this review we provide an in-depth analysis of conflicting reports regarding the impact of CXCR5CD8 T cells on antibody production and examine the data supporting a role for antibody-enhancement (B cell "helper") and antibody-downregulation (antibody-suppressor) by CXCR5CD8 T cell subsets.

Machine perfusion of kidney allografts affects early but not late graft function.

Background: Hypothermic machine perfusion (HMP) parameters are influenced by donor variables which further affect recipient outcome. Interplay between these parameters can help to predict kidney performance on pump and the long term outcome.

Methods: All the kidneys transplanted at our center between May 2013 through November 2017 were included in the study.

Facilitating Success of the Early Stage Surgeon Scientist Trainee: Growing the Surgeon Scientist Pipeline.

Objective: Surgeon scientists bring to bear highly specialized talent and innovative and impactful solutions for complicated clinical problems. Our objective is to inform and provide framework for early stage surgeon scientist training and support.

Summary Of Background Data: Undergraduate, medical student, and residency experiences impact the career trajectory of surgeon scientists.

The impact of donor and recipient diabetes on renal transplant outcomes.

The use of diabetic kidneys is increasing worldwide with better outcome than being on waitlist and possible reversal of diabetic changes in transplanted kidneys. But particular caution is warranted in diabetic donor-recipient combination. Total 1223 deceased donor kidney transplants were performed at our center between 2008 and 2018.

"Early" and "Late" Hospital readmissions in the first year after kidney transplant at a single center.

Background: Hospital readmission (HR) after surgery is considered a quality metric.

Methods: Data on 2371 first-time adult kidney transplant (KT) recipients were collected to analyze the "early" (≤30 days) and "late" (31-365 days) HR patterns after KT at a single center over a 12-year time span (2002-2013).

Results: 30-day, 90-day, and 1-year HR were 31%, 41%, and 53%, respectively.

Inverse Association Between the Quantity of Human Peripheral Blood CXCR5+IFN-γ+CD8+ T Cells With De Novo DSA Production in the First Year After Kidney Transplant.

Background: We recently reported that a novel CXCR5IFN-γCD8 T-cell subset significantly inhibits posttransplant alloantibody production in a murine transplant model. These findings prompted the current study to investigate the association of human CD8 T cells with the same phenotype with the development of de novo donor-specific antibody (DSA) after kidney transplantation.

Methods: In the current studies, we prospectively and serially analyzed peripheral blood CD8 and CD4 T-cell subsets and monitored for the development of de novo DSA in kidney transplant recipients during the first-year posttransplant.

Obesity, transplantation, and bariatric surgery: An evolving solution for a growing epidemic.

The increasing obesity epidemic has major implications in the realm of transplantation. Patients with obesity face barriers in access to transplant and unique challenges in perioperative and postoperative outcomes. Because of comorbidities associated with obesity, along with the underlying end-stage organ disease leading to transplant candidacy, these patients may not even be referred for transplant evaluation, much less be waitlisted or actually undergo transplant.

Antibody-suppressor CD8+ T Cells Require CXCR5.

Background: We previously reported the novel activity of alloprimed CD8 T cells that suppress posttransplant alloantibody production. The purpose of the study is to investigate the expression and role of CXCR5 on antibody-suppressor CD8 T-cell function.

Methods: C57BL/6 mice were transplanted with FVB/N hepatocytes.

Critical Role of Macrophage FcγR Signaling and Reactive Oxygen Species in Alloantibody-Mediated Hepatocyte Rejection.

Humoral alloimmunity negatively impacts both short- and long-term cell and solid organ transplant survival. We previously reported that alloantibody-mediated rejection of transplanted hepatocytes is critically dependent on host macrophages. However, the effector mechanism(s) of macrophage-mediated injury to allogeneic liver parenchymal cells is not known.

Unique CD8+ T Cell-Mediated Immune Responses Primed in the Liver.

Background: The liver immune environment is tightly regulated to balance immune activation with immune tolerance. Understanding the dominant immune pathways initiated in the liver is important because the liver is a site for cell transplantation, such as for islet and hepatocyte transplantation. The purpose of this study is to examine the consequences of alloimmune stimulation when allogeneic cells are transplanted to the liver in comparison to a different immune locale, such as the kidney.

mTOR Inhibition Suppresses Posttransplant Alloantibody Production Through Direct Inhibition of Alloprimed B Cells and Sparing of CD8+ Antibody-Suppressing T cells.

Background: De novo alloantibodies (donor-specific antibody) contribute to antibody-mediated rejection and poor long-term graft survival. Because the development of donor-specific antibody is associated with early graft loss of cell transplants and reduced long-term survival of solid organ transplants, we hypothesized that conventional immunosuppressives, calcineurin inhibitors (CNi), and mammalian target of rapamycin inhibitors (mTORi), may not be as effective for suppression of humoral alloimmunity as for cell-mediated immunity.

Methods: Wild-type or CD8-depleted mice were transplanted with allogeneic hepatocytes.

Early immunosuppression treatment correlates with later de novo donor-specific antibody development after kidney and pancreas transplantation.

Background: De novo donor-specific antibodies (dnDSA) post-transplant correlate with a higher risk of immunologic graft injury and loss following kidney and pancreas transplantation. Post-transplant dnDSA can occur within the first post-transplant year.

Methods: In this study, 817 of 1290 kidney and simultaneous kidney/pancreas recipients were tested for dnDSA post-transplant.

Cytotoxic effector function of CD4-independent, CD8(+) T cells is mediated by TNF-α/TNFR.

Background: Liver parenchymal cell allografts initiate both CD4-dependent and CD4-independent, CD8(+) T cell-mediated acute rejection pathways. The magnitude of allospecific CD8(+) T cell in vivo cytotoxic effector function is maximal when primed in the presence of CD4(+) T cells. The current studies were conducted to determine if and how CD4(+) T cells might influence cytotoxic effector mechanisms.

Inhibition of recall responses through complementary therapies targeting CD8+ T-cell- and alloantibody-dependent allocytotoxicity in sensitized transplant recipients.

Allospecific T memory cell responses in transplant recipients arise from environmental exposure to previous transplantation or cross-reactive heterologous immunity. Unfortunately, these memory responses pose a significant barrier to the survival of transplanted tissue. We have previously reported that concurrent inhibition of CD154 and LFA-1 suppresses primary CD8-dependent rejection responses that are not controlled by conventional immunosuppressive strategies.

Twenty-five year evolution of kidney transplantation at the Ohio State University.

Over the course of the last 25 years, we have seen dramatic improvements in the outcomes following kidney transplantation at The Ohio State University. With the employment of each new pharmacologic or biologic agent, came a reduction in the incidence of acute rejection within the first post-transplant year and beyond as reported in these analyses. This dramatic reduction in acute rejection over progressive eras translated into significantly improved graft survivals.