Recurrent Autoimmune Diseases Research Articles

Hemophagocytic lymphohistiocytosis secondary to virus infection and followed by lupus nephritis recurrence in a renal transplantation pediatric recipient: a case report

BackgroundHemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening disorder characterized by systemic inflammation and organ failure as a result of dysregulated immune cell activation. HLH can be induced by a variety of factors including infection, tumours and autoimmune disease and can also occur in patients following solid organ transplantation. Occurrence of HLH and lupus nephritis (LN) successively within a short period of time after renal transplantation is uncommon.Case presentationWe described an 11-year-old female post-transplant patient who presented with hemocytopenia, fever, elevated serum ferritin, splenomegaly, hyperlipidemia, and hypofibrinemia, and was clinically diagnosed with HLH. After comprehensive treatment with corticosteroids, intravenous immunoglobulin (IVIG), and reducing immunosuppressants, her condition improved, but then hematuria ensued. The transplant kidney biopsy showed LN. She was treated with hydroxychloroquine and methylprednisolone while intensive immunosuppressive agents were given. She has remained in remission for two years until now.ConclusionsThe main inducing factors of HLH should be identified as early as possible, and accurate treatment plans should be taken. The long-course IVIG regimen may be one of the effective treatments for virus-induced HLH. After remission of HLH, we need to be alert to the recurrence of autoimmune diseases in patients with underlying diseases, and timely increase immunosuppressants.

Integrated Bioinformatics Analysis and Experimental Verification of Immune Cell Infiltration and the Related Core Genes in Ulcerative Colitis.

Ulcerative colitis is a recurrent autoimmune disease. At present, the pathogenesis of UC is not completely clear. Hence, the etiology and underlying molecular mechanism need to be further investigated. Three sets of microarray datasets were included from the Gene Expression Omnibus database. The differentially expressed genes in two sets of datasets were analyzed using the R software, and the core genes of UC were screened using machine learning. The sensitivity and specificity of the core genes were evaluated with the receiver operating characteristic curve in another microarray dataset. Subsequently, the CIBERSORT tool was used to analyze the relationship between UC and its core genes and immune cell infiltration. To verify the relationship between UC and core genes and the relationship between core genes and immune cell infiltration in vivo. A total of 36 DEGs were identified. AQP8, HMGCS2, and VNN1 were determined to be the core genes of UC. These genes had high sensitivity and specificity in receiver operating characteristic curve analysis. According to the analysis of immune cell infiltration, neutrophils, monocytes, and macrophages were positively correlated with UC. AQP8, HMGCS2, and VNN1 were also correlated with immune cell infiltration to varying degrees. In vivo experiments verified that the expressions of neutrophils, monocytes, and macrophages increased in the UC colon. Furthermore, the expressions of AQP8 and HMGCS2 decreased, whereas that of VNN1 increased. Azathioprine treatment improved all the indicators to different degrees. AQP8, HMGCS2, and VNN1 are the core genes of UC and exhibit different degrees of correlation with immune cells. These genes are expected to become new therapeutic targets for UC. Moreover, the occurrence and development of UC are influenced by immune cell infiltration.

Cognitive impairment of MRL mice is related to NMDA receptor-mediated inflammatory response and production of adhesion molecules in MRL/lpr mice-derived micro-vascular endothelial cells.

Systemic lupus erythematosus (SLE) is a chronic recurrent autoimmune disease affecting almost all organs. This study was conducted to investigate cognitive impairment of SLE mice (MRL/lpr mice), and explore associated pathological mechanism. Behavior tests (open-field test, elevated plus-maze test, forced swimming test, sucrose preference test, and Morris water maze test) were conducted in MRL/MPJ and MRL/lpr mice. ELISA test was performed to determine levels of antibodies (anti-dsDNA, anti-RPA, anti-ACA, and anti-NR2a/b) and inflammatory factors [tumour necrosis factor a (TNF-a), interleukin (IL)-6, IL-8, and IL-10]. Micro-vascular endothelial cells (MVECs) were isolated, identified, and divided into MVECs (NC), anti-NR2a/2b, memantine, glycine, dexamethasone, and IL-1b groups. Cell proliferation was measured using cell counting kit-8 (CCK-8) assay, and Western blotting was applied to evaluate ELAM-1, VCAM-1, ICAM-1, IKBa, p-IKBa expression. MRL/lpr mice demonstrated lower locomotion/exploration ability, higher anxiety, obvious depression symptoms, lower learning/memory capability compared with MRL/MPJ mice. MRL/lpr mice demonstrated high levels of anti-NR2a/b antibody and auto-antibodies. NMDA receptor antagonist (memantine) significantly increased, and NMDA receptor agonist (glycine) significantly decreased MVECs proliferation compared with NC group ( p < 0.05). Memantine significantly reduced and glycine predominantly enhanced TNF-a, IL-6, IL-8, and IL-10 levels compared with NC group ( p < 0.05). NMDA receptor antagonist and agonist modulated adhesion molecules expression in MVECs. ELAM-1, VCAM-1, and ICAM-1 expressions were significantly down-modulated in memantine group, and remarkably up-modulated in glycine group compared with NC group ( p < 0.05). NMDA receptor antagonist and agonist regulated phosphorylation of p-IKBa. The above effects of memantine evenly equaled to dexamethasone, and glycine evenly equaled to IL-1b. In conclusion, cognitive impairment of MRL mice might be associated with NMDA receptor-mediated inflammatory response and production of adhesion molecules in MRL/lpr mice-derived MVECs.

Relapse of autoimmune diseases after liver transplantation

Background. The recurrence of autoimmune liver diseases can lead to reduced survival of recipients and grafts.Aim. To study the incidence and impact of the recurrence of autoimmune liver diseases on graft survival; the effect of maintenance immunosuppression on the recurrence of autoimmune diseases in liver transplant recipientsMaterial and methods. Transplantation outcomes in 111 recipients (21 recipients operated on for autoimmune hepatitis, 50 recipients operated on for primary biliary cirrhosis, and 40 recipients operated on for primary sclerosing cholangitis) were analyzed retrospectively.Results. The recurrence of autoimmune hepatitis is observed in 5%, the recurrence of primary biliary cirrhosis is in 10%, and the recurrence of primary sclerosing cholangitis is in 17% of cases. Among patients with recurrence of autoimmune diseases, men accounted for 54%, while for only 31% in the subgroup of patients without relapse (p=0.004). The followup for recipients with relapse (64.5 (42.8;82.0) months) was comparable to the follow-up for recipients without relapse (46.5 (17.9;103.5) months, p=0.54). A ten-year graft survival was significantly higher in the group of recipients with recurrent autoimmune diseases compared with recipients without autoimmune diseases recurrence (p&lt;0.0001).Conclusions. The recurrence of autoimmune diseases leads to a decrease in graft survival. The effect of immunosuppression components on the risk of recurrence of autoimmune diseases in the graft has not been established.

Total alopecia and vascular malformation: a random association or a prognostic factor?

Background. Alopecia areata (AA) is a chronic recurrent autoimmune disease that leads to a deterioration in the quality of life. And capillary malformation (CM) occurs in 1/3 of AA patients.&#x0D; Aim. To identify the connection of one of the forms of AA with CM in the occipital region.&#x0D; Materials and methods. 18 patients with total alopecia (TA), 5 men and 13 women were under observation. The age ranged from 26 to 58 years, the duration of the disease ranged from 1 to 29 years. To determine the relationship between CM and TA, the odds ratio was used with the corresponding 95% confidence intervals.&#x0D; Results. The study showed the occurrence of CM in patients with TA in 94.4%. The correlation of CM and TA turned out to be statistically significant in comparison with the control group.&#x0D; Conclusion. The results indicate that there is a reliable relationship between CM and TA, which allows us to conclude that CM is associated with severe forms of alopecia. In addition, CM can be a valuable marker and prognostic factor indicating the development of more severe forms and course of AA.

Non-Immunologic Causes of Late Death-Censored Kidney Graft Failure: A Personalized Approach.

Despite continuous advances in surgical and immunosuppressive protocols, the long-term survival of transplanted kidneys is still far from being satisfactory. Antibody-mediated rejection, recurrent autoimmune diseases, and death with functioning graft are the most frequent causes of late-kidney allograft failure. However, in addition to these complications, a number of other non-immunologic events may impair the function of transplanted kidneys and directly or indirectly lead to their failure. In this narrative review, we will list and discuss the most important nonimmune causes of late death-censored kidney graft failure, including quality of the donated kidney, adherence to prescriptions, drug toxicities, arterial hypertension, dyslipidemia, new onset diabetes mellitus, hyperuricemia, and lifestyle of the renal transplant recipient. For each of these risk factors, we will report the etiopathogenesis and the potential consequences on graft function, keeping in mind that in many cases, two or more risk factors may negatively interact together.

Trifolirhizin regulates the balance of Th17/Treg cells and inflammation in the ulcerative colitis mice through inhibiting the TXNIP-mediated activation of NLRP3 inflammasome.

Ulcerative colitis (UC) is a chronic and recurrent autoimmune disease, characterized by recurrence and remission of mucosal inflammation. Although the understanding of the pathogenesis of UC has been improved, effective therapeutic drugs are required for treating patients with UC. In current work, the mouse model of colitis was established. Trifolirhizin was demonstrated to improve symptom in dextran sulfate sodium (DSS)-induced colitis mice. The body weight of mice was elevated, whereas the disease activity index (DAI) was reduced. Moreover, trifolirhizin was involved in inhibition of inflammation and regulation of the balance of T helper 17 (Th 17) cells and regulatory T (Treg) cells in DSS-induced colitis mice. Further, the activation NLRP3 inflammasome was suppressed by trifolirhizin in DSS-induced colitis mice. Trifolirhizin was also identified to regulate AMP-activated protein kinase (AMPK)-thioredoxin-interacting protein (TXNIP) pathway. The trifolirhizin-mediated anti-inflammatory effect was inhibited by suppressing AMPK in DSS-induced UC mice. In summary, the research suggested that administration of trifolirhizin significantly improved the symptoms and the pathological damage in DSS-induced UC mice. Trifolirhizin regulated the balance of Th17/Treg cells and inflammation in the UC mice through inhibiting the TXNIP-mediated activation of NLRP3 inflammasome.

Ankylosing spondylitis in combination with Crohn's disease: clinical case

Introduction. Ankylosing spondylitis and Crohn's disease are chronic recurrent autoimmune diseases. In case of a combined course their activity tends to progress, regardless of the phase of the underlying disease.The aim of the study. To analyze the combination of ankylosing spondylitis and Crohn's disease, issues of its diagnosis and selection of therapy.Results. The combination of ankylosing spondylitis and Crohn's disease tend to progress independently, regardless of the phase of the underlying disease. The main problem that complicates diagnosis is the lack of a unifed approach to the defnition of extra skeletal and extraintestinal manifestations.Conclusion. The management of patients with a combination of ankylosing spondylitis and Crohn's disease is a common problem of rheumatologists and gastroenterologists. An interdisciplinary approach will allow timely diagnosis of extra-skeletal and extra-intestinal manifestations and correct therapy.

PSC recurrence post liver transplantation: retransplantation justified or not?

Post-liver transplant (LT), primary disease recurrence is a major cause of graft failure and long-term patient mortality (1). For decades, hepatitis C virus (HCV) recurrence was the number one cause of graft loss (2); however, with the development of potent anti-viral therapy, HCV transplant recipients no longer experience graft loss and death. In contrast, recurrence of autoimmune disease - particularly Primary Sclerosing Cholangitis (PSC) - remains a valid concern for the liver transplant community. This is despite an excellent short-term outcome post LT, with a survival rate above 90 % within the first year after transplant (3).

Homoeopathy a boon for rheumatoid arthiritis

Bone is the important part of our body, without bone there is no existence of human body. Bone is the frame of a human body; The whole-body structure depends upon bone. Any disease related to bone and related structure will lead to one of the leading disorders of bone that is RHEUMATOID ARTHIRITIS. Rheumatoid Arthritisis an auto-immune enlightened disorder of cartilage degeneration, inflammation, and affects joint lining causing painful swelling. Rheumatoid Arthritis leads to pain, disability as well as difficulty in joints and restricts the routine movements of human being. Rheumatoid Arthritis is most common rheumatic disease; Limitation of controversial medicine management of this condition indicates the real need to safe and effective treatment of osteoarthritis. In Homoeopathy there is lots of scope for the treatment of this disease because homoeopathy follows the nature of law similia similibus curenture and treats the person as a whole by doing the individualization and selecting the constitutional medicine and stops the recurrence of auto-immune diseases like Rheumatoid Arthritis, psoriasis and others without other suffering and side effects.

RETRACTED: Amelioration of imiquimod-induced psoriasis-like dermatitis in mice by DSW therapy inspired hydrogel

Psoriasis is a long-lasting and recurrent autoimmune disease which is incurable so far. Dead Sea water (DSW) therapy is an effective approach to help control the symptoms of psoriasis due to the abundant mineral ions in DSW, which inspired the material formulation in this study. Rubidium–Sodium alginate/Polyacrylamide hydrogels (Rb-SA/PAAm gels) composed of sodium alginate and polyacrylamide interpenetrating network structure with different concentrations of rubidium and certain magnesium and zinc content were prepared for the treatment of psoriasis. The obtained results suggest the good mechanical properties of the Rb-SA/PAAm gels including toughness and swelling performance. In terms of in vitro tests, the Rb-SA/PAAm gels not only show nontoxicity to human keratinocyte cell line (Hacats) but also inhibits the activity against inflammatory NF-κβ signaling pathway. Meanwhile, they can release Rb+ which enable the Rb-SA/PAAm gels have better antibacterial ability to Streptococcus and Escherichia coli. The results obtained from in vivo tests indicate that these hydrogels could alleviate the symptoms of psoriasis caused by Imiquimod (IMQ) in mice by reducing the inflammatory factor in STAT3 pathway and therefore reduce the immune stimulation of the spleen. In conclusion, the 100Rb-SA/PAAm gel has demonstrated great potential to be a topical wettable dressing for psoriasis treatment.

Modeling and analysis of recurrent autoimmune disease

In this paper, we consider dynamics and bifurcations in two HIV models with cell-to-cell interaction. The difference between the two models lies in the inclusion or omission of the effect of involvement. Particular attention is focused on the effects due to the cell-to-cell transmission and the effect of the involvement. We investigate the local and global stability of equilibria of the two models and give a comparison. We derive the existence condition for Hopf bifurcation and prove no Bogdanov-Takens bifurcation in this system. In particular, we show that the system exhibits the recurrence phenomenon, yielding complex dynamical behavior. It is also shown that the effect of the involvement is the main cause of the periodic symptoms in HIV or malaria disease. Moreover, it is shown that the increase of cell-to-cell interaction may be the main factor causing Hopf bifurcation to disappear, and thus eliminating oscillation behavior. Finally, numerical simulations are present to demonstrate our theoretical results.

Dihydroartemisinin ameliorates psoriatic skin inflammation and its relapse by diminishing CD8+ T-cell memory in wild-type and humanized mice.

Conventional immunosuppressants cause side effects and do not prevent the recurrence of autoimmune diseases. Moreover, they may not inhibit autoimmunity mediated by pathogenic memory T-cells. Dihydroartemisinin (DHA) has been shown to regulate autoimmunity. However, it remains unknown whether DHA impacts psoriasis and its recurrence. The objective of this study was to determine therapeutic effects of DHA on psoriasis and its relapse as well as its underlying mechanisms.Methods: We established animal models of imiquimod (IMQ)-induced psoriasis-like wild-type mice and humanized NSG mice receiving lesional human skin from patients with psoriasis. Many immunoassays, including immunohistochemistry, flow cytometry, quantitative RT-PCR and Western blotting, were performed.Results: We found that DHA not only ameliorated acute skin lesion of psoriatic mice, but also alleviated its recurrence by diminishing CD8+ central memory T (TCM) and CD8+ resident memory T (TRM) cells. It attenuated epidermal pathology and T-cell infiltration in the skin of IMQ-induced psoriatic mice while suppressing expression of IL-15, IL-17 and other proinflammatory cytokines in the skin. Surprisingly, DHA reduced the frequency and number of CD8+, but not CD4+, subset of CD44highCD62Lhigh TCM in psoriatic mice, whereas methotrexate (MTX) lowered CD4+, but not CD8+, TCM frequency and number. Indeed, DHA, but not MTX, downregulated eomesodermin (EOMES) and BCL-6 expression in CD8+ T-cells. Furthermore, DHA, but not MTX, reduced the presence of CD8+CLA+, CD8+CD69+ or CD8+CD103+ TRM cells in mouse skin. Interestingly, treatment with DHA, but not MTX, during the first onset of psoriasis largely prevented psoriasis relapse induced by low doses of IMQ two weeks later. Administration of recombinant IL-15 or CD8+, but not CD4+, TCM cells resulted in complete recurrence of psoriasis in mice previously treated with DHA. Finally, we demonstrated that DHA alleviated psoriatic human skin lesions in humanized NSG mice grafted with lesional skin from psoriatic patients while reducing human CD8+ TCM and CD103+ TRM cells in humanized mice.Conclusion: We have provided the first evidence that DHA is advantageous over MTX in preventing psoriasis relapse by reducing memory CD8+ T-cells.

Application of active components from traditional Chinese medicine in treatment of inflammatory bowel disease

Inflammatory bowel disease(IBD) is a non-specific and chronic recurrent autoimmune disease that involves the gastrointestinal tract. Clinical symptoms of intestinal bleeding, diarrhea, and weight loss threat to human health and induce colorectal cancer. The pathogenesis included living environment, genetic factors, immune cell infiltration and immune stress, weakened mucosal barrier defense and intestinal flora imbalance. At present, clinical treatment drugs mainly include aminosalicylic acid, corticosteroids, immunosuppressants, biological agents, etc., in view of the disadvantages of poor therapeutic effect and expensive price. The active ingredients of traditional Chinese medicine(TCM) in the treatment IBD have various biological activities and multiple targets such as anti-inflammatory, antibacterial, anti-tumor and immune regulation. This article summarized the application and the research progress in protecting intestinal epithelial barrier, maintaining intestinal microbial homeostasis, inhibiting causative factors, and regulating Th1/Th17/Treg balance about TCM in the treatment of IBD. The review provided new ideas for further development of the new drugs on the mechanism based on active ingredients of TCM in IBD treatment.

Research Progress on the Establishment of Animal Model with Immune Thrombocytopenic Purpura - Review

Immune thrombocytopenic purpura (ITP) is a chronic and recurrent autoimmune disease, which seriously affects the life quality of patients. At present, a series of new advances have been made in the pathogenesis of ITP, particularly, in the abnormal cellular immunity. However, in the medical studiess generally research of ITP cellular immunity was limited. Therefore, it is urgent to establish an ideal ITP model for the study of ITP pathogenesis, so as to contribute to promote the ITP new treatment progeamme. In this review, the passive modeling inclinding anti-platelet serum modeling, monoclonal antiboty modeling, and active modeling including NZW× BXSB rat modeling, antigenic mimicry modeling, immune splenic cell transplantation modeling, transgenic model, fetal and neonatal allsimmune thrombocytopenia modeling and so on, are summarized.

Increased Complement 3a Receptor is Associated with Behcet\u2019s disease and Vogt-Koyanagi-Harada disease

Behcet’s disease (BD) and Vogt-Koyanagi-Harada disease (VKH) are systemic and recurrent autoimmune diseases associated with abnormal T cell immune response. Complement 3a receptor (C3aR) and complement 5a receptor (C5aR) have been reported to be involved in T cell mediated autoimmune disease. This study aimed to investigate the role of C3aR and C5aR in these two diseases. The C3aR expression in PBMCs was increased in patients with active BD (aBD) and active VKH (aVKH). No statistical difference was found concerning the expression of C5aR in PBMCs between patients with aBD or aVKH and normal controls. After the intraocular inflammation in BD and VKH patients was controlled, the C3aR expression returned back to normal levels. The serum from patients with aBD and aVKH significantly induced C3aR expression by PBMCs. C3a induced IL-6, IL-1β and TNF-α secretion, while inhibited the production of IL-10 by monocytes. Activation of C3aR in CD4+T cells could upregulate IL-17 production and inhibit IL-10 production, but had no detectable influence on IFN-γ production. Our data indicates that increased C3aR expression may lead to over activation of the Th17 cell response and may therefore contribute to the pathogenesis of BD and VKH disease.

The prospects of the biotherapy for refractory uveitis

Noninfectious uveitis is a kind of recurrent autoimmune disease and a major cause of blindness in clinical practice. Corticosteroids are the conventional medication, but have severe side effects for long-term users, and some refractory patients are treated with immunosuppressive agents. Because the pathogenesis of uveitis is related to the autoimmune imbalance mediated by CD4 + T lymphocytes. The macrophages, lymphocytes and some cytokines are involved. The immunomodulatory therapy is targeted to block the lymphocytes, cytokines or their receptors, so as to control the inflammatory damage or minimize the recurrence of the disease. The biological agents include the anti-tumor necrosis factor agents, interferon-α, interleukin receptor antagonists, cytotoxic T lymphocyte associated antigen fusion proteins and CD20 chimeric antibody. They bring a hope for the treatment of the patients with refractory uveitis. Because of the limited number of randomized clinical trials and patients, the indications, long-term effects, safety and side effects of these biologics need to be observed. In this article, the experiments and clinical trials of these new biologics for the treatment of uveitis in recent years are reviewed. (Chin J Ophthalmol, 2016, 52: 551-556).

First-Degree Living-Related Donor Liver Transplantation in Autoimmune Liver Diseases.

Liver transplantation (LT) is the treatment of choice for end-stage autoimmune liver diseases. However, the underlying disease may recur in the graft in some 20% of cases. The aim of this study is to determine whether LT using living donor grafts from first-degree relatives results in higher rates of recurrence than grafts from more distant/unrelated donors. Two hundred sixty-three patients, who underwent a first LT in the Toronto liver transplant program between January 2000 and March 2015 for autoimmune liver diseases, and had at least 6 months of post-LT follow-up, were included in this study. Of these, 72 (27%) received a graft from a first-degree living-related donor, 56 (21%) from a distant/unrelated living donor, and 135 (51%) from a deceased donor for primary sclerosing cholangitis (PSC) (n = 138, 52%), primary biliary cholangitis (PBC) (n = 69, 26%), autoimmune hepatitis (AIH) (n = 44, 17%), and overlap syndromes (n = 12, 5%). Recurrence occurred in 52 (20%) patients. Recurrence rates for each autoimmune liver disease were not significantly different after first-degree living-related, living-unrelated, or deceased-donor LT. Similarly, time to recurrence, recurrence-related graft failure, graft survival, and patient survival were not significantly different between groups. In conclusion, first-degree living-related donor LT for PSC, PBC, or AIH is not associated with an increased risk of disease recurrence.

Hopf and Generalized Hopf Bifurcations in a Recurrent Autoimmune Disease Model

This paper is concerned with bifurcation and stability in an autoimmune model, which was established to study an important phenomenon — blips arising from such models. This model has two equilibrium solutions, disease-free equilibrium and disease equilibrium. The positivity of the solutions of the model and the global stability of the disease-free equilibrium have been proved. In this paper, we particularly focus on Hopf bifurcation which occurs from the disease equilibrium. We present a detailed study on the use of center manifold theory and normal form theory, and derive the normal form associated with Hopf bifurcation, from which the approximate amplitude of the bifurcating limit cycles and their stability conditions are obtained. Particular attention is also paid to the bifurcation of multiple limit cycles arising from generalized Hopf bifurcation, which may yield bistable phenomenon involving equilibrium and oscillating motion. This result may explain some complex dynamical behavior in real biological systems. Numerical simulations are compared with the analytical predictions to show a very good agreement.

Exploiting T cell co-inhibition to delay autoimmune disease recurrence

Abstract Type 1 diabetes (T1D) results from T cell-mediated destruction of insulin-producing pancreatic β cells. Individuals with long-term disease are at risk of developing life-threatening complications. β cell replacement is a therapy for T1D but is limited by recurrent autoreactive T cell targeted β cell death. Thus, β cells better equipped to inhibit local T cell responses may survive longer in autoimmune recipients. Programmed-death 1 (PD-1) signaling through its ligand PD-L1 inhibits T cells, and may serve as a prominent defense in T1D. Using flow cytometric analysis, in the absence of T cells in NOD.RAG−/− mice we do not detect β cell PD-L1 expression. However, with T cells, we observed an increased proportion of β cells expressing PD-L1 in female non-obese diabetic (NOD) mice which had not developed diabetes. In addition, the majority of remaining live β cells at diabetes onset in NOD mice continue to express high levels of PD-L1. These three situations suggest that islet β cells may increase PD-L1 expression as a last line of defense to limit infiltrating T cell mediated destruction. To manipulate β cell PD-L1 expression prior to transplantation, we screened a panel of diabetes-related cytokines and found that IFN-γ enhances β cell PD-L1 expression. Unfortunately, islet transplant survival was not prolonged, which we hypothesized was due to enhanced MHC class I expression, facilitating CD8+ T cell-mediated killing. We therefore de-coupled PD-L1 from enhanced MHC I expression. Using this approach, enforced β cell PD-L1 expression delays disease recurrence. These data support our hypothesis that β cells expressing T cell co-inhibitory molecules, like PD-L1, can locally inhibit autoreactive T cells which may prevent transplant destruction.