Transplant immunology最新文献

{"title":"Survey of prevalence of BKV and JCV infections in pediatric heart transplant recipients","authors":"Fatemeh Gabeleh ,&nbsp;Mohammad Mahdavi ,&nbsp;Mohammad Hadi Karbalaie Niya ,&nbsp;Mehri Amiri ,&nbsp;Mehrdad Ravanshad","doi":"10.1016/j.trim.2025.102243","DOIUrl":"10.1016/j.trim.2025.102243","url":null,"abstract":"<div><h3>Background</h3><div>The Administration of anti-rejection medications in solid organ recipients may increase the risk of acquiring multiple infections. This study aimed to diagnose and monitor BKV and JCV viral infections in pediatric heart transplant recipients.</div></div><div><h3>Methods</h3><div>A cohort of 28 children, all under 18 years old, undergoing heart transplants was studied. Plasma and urine samples were collected, followed by DNA extraction and molecular testing to quantify viral loads. Demographic and clinical information were recorded and analyzed.</div></div><div><h3>Results</h3><div>The BK and JC viruria frequency among the cohort was 41.7 % and 12.5 %, respectively. No instances of BKV and JCV viremia were detected. The BKV DNA viral loads ranged from 3.1 × 10² to 11.8 × 10⁶ copies/mL, while the JC viruria viral load ranged from 1.1 × 10² to 13.6 × 10⁶ copies/mL. BKV-JCV co-infection was identified in 12.5 % of patients.</div></div><div><h3>Conclusions</h3><div>Considering a high prevalence of BKV viruria in the recruited patients, clinicians should be well acquainted with the steps involved in the diagnosis and management of polyomaviral infections.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"91 ","pages":"Article 102243"},"PeriodicalIF":1.6,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144120941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Successful treatment of very severe aplastic anemia with double unrelated umbilical cord blood transplantation in a donor-specific antigen positive adult patient: A case report and review","authors":"Meng Lu ,&nbsp;Jia-yan Leng ,&nbsp;Chen-yun Xu ,&nbsp;Chao-ran Lv ,&nbsp;Zhen Qian ,&nbsp;Yan Zhou ,&nbsp;Di Yu ,&nbsp;Jun Qian","doi":"10.1016/j.trim.2025.102241","DOIUrl":"10.1016/j.trim.2025.102241","url":null,"abstract":"<div><div>To overcome the cell-dose barrier of cord blood, double unrelated umbilical cord blood transplantation (UCBT) has become increasingly common in adults with severe aplastic anemia (SAA). Pre-existing donor-specific anti-HLA antibodies (DSAs) represent a risk factor for graft failure (GF). Desensitization therapy should be conducted to reduce circulating DSA levels, thereby decreasing the risk of GF. This report details a case of a female patient with acquired SAA and pre-transplantation anti-HLA antibodies. Desensitization with rituximab, intravenous immunoglobulin (IVIG), and plasma exchange (PE) was performed before transplantation with a conditioning regimen of fludarabine (30 mg/m² for six days) and cyclophosphamide (50 mg/kg/d for four days). DSA titers were significantly reduced; the patient was successfully treated with double unrelated UCBT. Currently, complete remission (CR) status has been maintained for over a year after UCBT, with no signs of graft-vs-host disease. Our findings support the use of double-unit unrelated UCBT in adult patients with SAA when cell doses of single-unit UCB are inadequate. Monitoring and reducing DSA levels before and after UCBT is an efficient way to reduce the risk of GF.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"91 ","pages":"Article 102241"},"PeriodicalIF":1.6,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144080299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The impact of ABO compatibility/incompatibility between donor and recipient of allogeneic bone marrow transplant on transplant outcomes","authors":"Ehsan Yazdandoust ,&nbsp;Abbas Hajifathali ,&nbsp;Amir Teimourpour ,&nbsp;Sedigheh Amini-Kafiabad ,&nbsp;Elham Roshandel","doi":"10.1016/j.trim.2025.102231","DOIUrl":"10.1016/j.trim.2025.102231","url":null,"abstract":"<div><h3>Background</h3><div>ABO blood group mismatch between donor and recipients is not considered as a major contraindication to allogeneic hematopoietic stem cell transplantation (allo-HSCT). Nevertheless, there is still conflicting reports on the impact of ABO incompatibility on allo-HSCT outcomes, including the risk of graft-versus-host disease (GVHD), relapse of underlying disease, and patient survivals.</div></div><div><h3>Methods</h3><div>We conducted a retrospective cohort study in 157 patients who underwent HSCT from October 1st 2019, to September 30th 2023, to determine the effect of ABO compatibility on allo-HSCT outcomes, as evaluating for pure red cell aplasia, engraftment time/status, chronic/acute allo-GVHD, and non-relapse mortality.</div></div><div><h3>Results</h3><div>Overall, 50.3 % of HSCT patients were ABO incompatible and 49.7 % of allo-HSCT patients were ABO compatible. Our findings suggest that the risk of pure red cell aplasia was significantly higher in cases with the major and bidirectional ABO incompatibility (<em>P</em> &lt; 0.001) with odds ratio (OR): 19.8 [95 % confidence interval (CI): 2.3–2578.9; P &lt; 0.001), and anti-A isohemagglutinin against donor red blood cells (RBCs) in the recipient serum is an important risk factor for this complication. Our results do not show any significant relationship between ABO incompatibility/compatibility on engraftment time and graft failure. The ABO incompatibility increased RBC transfusion burden but did not affect platelet consumption, the incidence and severity of acute and chronic GVHD, patient survivals and non-relapse mortality.</div></div><div><h3>Conclusion</h3><div>Our findings suggest that allo-HSCT with bidirectional ABO incompatibility with anti-A isohemagglutinins are associated with the occurrence of pure erythroid aplasia. However, ABO incompatibility did not affect the risk for acute and chronic GVHD, survival of patients, and all-HSCT engraftment status.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"91 ","pages":"Article 102231"},"PeriodicalIF":1.6,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143927462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma-circulating miR-638, miR-6511b-5p, miR-3613-5p, miR-455-3p, miR-5787, and miR-548a-3p as noninvasive biomarkers of immune reconstitution post-allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia patients","authors":"Marzieh Izadifard ,&nbsp;Mohammad Ahmadvand ,&nbsp;Bahram Chahardouli ,&nbsp;Mohammad Vaezi ,&nbsp;Ghasem Janbabai ,&nbsp;Ghazal Seghatoleslami ,&nbsp;Mehran Bahrami ,&nbsp;Marjan Yaghmaie ,&nbsp;Maryam Barkhordar","doi":"10.1016/j.trim.2025.102240","DOIUrl":"10.1016/j.trim.2025.102240","url":null,"abstract":"<div><h3>Introduction</h3><div>Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a viable treatment option for acute myeloid leukemia (AML), though it carries risks including delayed immune reconstitution and hematopoietic reconstitution failure. This study aimed to explore the potential of circulating miRNA levels as biomarkers for post-transplant immune reconstitution.</div></div><div><h3>Methods</h3><div>This observational study was carried out on de novo non-M3 AML patients receiving allo-HSCT from HLA-matched sibling donors at Shariati Hospital, Iran in 2020–2023. Accordingly, the immunophenotype of NK cells, T cells, and B cells was determined by ten-color multiparameter flow cytometry on blood samples collected pre-transplantation and at day +30 post-transplantation. Concurrently, plasma levels of miR-638, miR-6511b-5p, miR-3613-5p, miR-455-3p, miR-5787, and miR-548a-3p were quantified using quantitative reverse transcription–polymerase chain reaction (RT qPCR).</div></div><div><h3>Results</h3><div>The expression of miR-638, miR-3613-5p, miR-455-3p, and miR-548a-3p positively correlated with CD4⁺ T cells, CD4⁺/CD8⁺ T cell ratio, CD3⁻/16⁺/56⁻ cells, and platelet count. Elevated miR-455-3p and miR-3613-5p expressions were associated with higher CD3⁻/16⁺/56⁻ cells (<em>P</em> = 0.0475 and <em>P</em> = 0.0325, respectively). Similarly, miR-638 upregulation correlated with increases in CD4⁺ T cells (<em>P</em> = 0.0112) and the CD4⁺/CD8⁺ T cell ratio (<em>P</em> = 0.006), while miR-548a-3p upregulation was associated with increases in the CD4⁺/CD8⁺ T cell ratio (<em>P</em> = 0.0353) and platelet count (<em>P</em> = 0.0191). Conversely, miR-3613-5p and miR-6511b-5p had considerable negative correlations with CD8⁺ T cells (P = 0.03 and <em>P</em> = 0.0246, respectively), whereas miR-5787 negatively correlated with CD3⁺/16⁻/56⁺ cells (<em>P</em> = 0.025).</div></div><div><h3>Conclusion</h3><div>Our findings suggest that differentiation of cell subpopulations is regulated by specific miRNAs. Furthermore, miRNA-based strategies may be developed for immunotherapeutic treatments of AML.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"91 ","pages":"Article 102240"},"PeriodicalIF":1.6,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144033467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predictive modeling for organ transplant rejection: The promising role of artificial intelligence and machine learning","authors":"Tarun Kumar Suvvari","doi":"10.1016/j.trim.2025.102223","DOIUrl":"10.1016/j.trim.2025.102223","url":null,"abstract":"","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"90 ","pages":"Article 102223"},"PeriodicalIF":1.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143711418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"“Virtual crossmatch reveals donor-specific MICA antibodies in antibody mediated rejection: First established Indian case”","authors":"Machiraju Sai Ravi Shankar ,&nbsp;Mamidi Neeraja ,&nbsp;Mohit Chowdhry ,&nbsp;Ayushi Yadav ,&nbsp;Sriya Machiraju ,&nbsp;Meenakshi Singh ,&nbsp;Swarnalata Gowrishanker","doi":"10.1016/j.trim.2025.102229","DOIUrl":"10.1016/j.trim.2025.102229","url":null,"abstract":"<div><div>Kidney transplantation is the best treatment for patients with End-stage renal disease (ESRD), offering significant improvements in their survival and quality of life. However, immune-mediated rejection of the graft remains a critical challenge. Anti-Human Leukocyte Antigen (HLA) antibodies are well-recognized mediators of acute and chronic rejection. In contrast, the role of non-HLA antibodies particularly donor-specific Anti-MHC class I-related chain A (MICA) antibodies (dsMICA Abs) requires further investigation.</div><div>We report the first documented case in India of acute antibody-mediated rejection (AMR) in renal transplant recipients attributed to dsMICA. The patient, an 18-year-old male, developed graft dysfunction post-transplant despite a negative HLA Complement dependent Cytotoxicity crossmatch (CDCXM) and Lysate based Luminex Crossmatch (LumXm) results performed prior to transplantation. A more detailed diagnostic workup revealed the presence of dsMICA Abs, implicating them in the observed AMR. After a targeted treatment regimen of plasmapheresis and intravenous immunoglobulin (IVIG) therapy, the patient showed substantial clinical improvement, marked by declining creatinine levels and then restoration of renal function. This study underscores the clinical significance of dsMICA antibodies in AMR and advocates for the need for routine non-HLA antibody screening in addition to anti-HLA screening post-transplant immunological monitoring.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"90 ","pages":"Article 102229"},"PeriodicalIF":1.6,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143874286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Outcomes of CMV infection in the setting of gastrointestinal graft-vs.-host disease in the era of pre-emptive and prophylactic antiviral therapy","authors":"Meera Patel ,&nbsp;Supriya Singh ,&nbsp;Puneet Dhillon ,&nbsp;Sofia Molina Garcia ,&nbsp;Michael Sheu ,&nbsp;Sonya Kothadia ,&nbsp;Ali Mushtaq ,&nbsp;Aneela Majeed","doi":"10.1016/j.trim.2025.102232","DOIUrl":"10.1016/j.trim.2025.102232","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Concurrent cytomegalovirus infection (CMVi) and gastrointestinal graft-versus-host disease (GI-GVHD) poses significant risks for increased morbidity and mortality in patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT). Primary prophylaxis with letermovir therapy has been shown to decrease the risk of CMV reactivation, but studies examining this relationship after GI-GVHD are lacking. We reviewed our center's outcomes associated with concomitant CMVi and GI-GVHD before and after our adopting the use of letermovir therapy for CMV prophylaxis in 2017.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;This was a single-center, retrospective study of allo-HCT patients who developed GI-GVHD and CMVi between June 2013 and June 2021. CMVi was defined as detection of CMV in the blood or detection of CMV in sampled tissue. CMV colitis was defined as biopsy-proven tissue-invasive CMV disease. The primary outcome was one year survival.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;We evaluated 43 allo-HCT patients who had concomitant CMVi and GI-GVHD. Out of 43 patients, 40 of them (93 %) had a high risk serostatus for CMVi (recipient seropositive). CMV colitis was confirmed by biopsy in 18 patients (42 %) and was clinically suspected in 20 patients (47 %). Twenty-five patients (58 %) developed CMV viremia, and 18 of them developed concomitant biopsy proven CMV colitis. Nine patients (21 %) received letermovir therapy for primary CMV prophylaxis, and 7 of these 9 patients (78 %) developed breakthrough CMVi while receiving prophylaxis. The median time from HCT to CMVi was similar between the group that received letermovir prophylaxis and the group that did not. Median peak CMV levels were lower in the prophylaxis group. Overall survival rates at one and five years were 65 % and 21 %, respectively, with the mortality reaching 25 % at 164 days and 50 % at 480 days. There was no statistically significant difference in one year survival between patients with CMV viremia but without colitis compared to those with CMV viremia and colitis (&lt;em&gt;p&lt;/em&gt; = 0.648, 95 % CI 0.3–1.57). One-year survival was also not statistically different between patients who received letermovir prophylaxis compared to those who did not (&lt;em&gt;p&lt;/em&gt; = 0.250, 95 % CI 0.60–6.97) or between patients with high grade GI-GVHD (grade 3–4) and low-grade GI-GVHD (grade 1–2; &lt;em&gt;p&lt;/em&gt; = 0.277, 95 % CI 0.64–4.83).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;In this high-risk cohort with GI-GVHD and CMVi, the peak viral load was lower in the group that received letermovir prophylaxis, but the median time to onset of CMVi and survival were not statistically different. The majority of patients in the letermovir prophylaxis group developed CMVi while on letermovir. Further investigations with larger sample sizes may better assess the impact of letermovir therapy on patient survival and the development of CMVi outcomes in the setting of GI-GVHD in the era of pre-emptive prophyl","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"90 ","pages":"Article 102232"},"PeriodicalIF":1.6,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143874285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Drug-induced acute pancreatitis following dose increase of mycophenolate mofetil in a kidney transplant recipient: A case report and literature review","authors":"Maroun Abou-Jaoude ,&nbsp;Ahmed Elsidig ,&nbsp;Sara Abdel-Samad ,&nbsp;Ibrahim Tfayli","doi":"10.1016/j.trim.2025.102230","DOIUrl":"10.1016/j.trim.2025.102230","url":null,"abstract":"<div><h3>Background</h3><div>Mycophenolate Mofetil (MMF) is widely used as an immunosuppressive agent in transplant recipients but is rarely associated with acute pancreatitis.</div></div><div><h3>Case presentation</h3><div>We report the case of a 25-year-old male kidney transplant recipient with juvenile cystinosis who developed acute pancreatitis following an increase in MMF dosage from 500 mg to 750 mg twice daily. The patient had previously experienced complications post-transplant, including posterior reversible encephalopathy syndrome and BK virus-related urethral stricture. A recent episode of acute antibody-mediated rejection, confirmed by biopsy, led to the reintroduction and escalation of MMF alongside Tacrolimus. One month later, the patient presented with severe epigastric pain, vomiting, and diarrhea. Laboratory tests revealed markedly elevated lipase levels (2269 U/L), meeting the Atlanta criteria for acute pancreatitis. Imaging excluded alternative etiologies. The patient's symptoms and lipase levels improved immediately after reducing the MMF dose.</div></div><div><h3>Conclusion</h3><div>This case highlights the potential for MMF-induced pancreatitis, particularly following dose escalation, and underscores the importance of cautious dosing and close monitoring in transplant recipients.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"90 ","pages":"Article 102230"},"PeriodicalIF":1.6,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143859365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Allogenic stem cell transplantation response for relapsed or refractory Hodgkin lymphoma patients: An experience in Iran","authors":"Amineh Salem ,&nbsp;Mahshid Mehdizadeh ,&nbsp;Sayeh Parkhideh","doi":"10.1016/j.trim.2025.102228","DOIUrl":"10.1016/j.trim.2025.102228","url":null,"abstract":"<div><div>Stem cell transplantation (SCT) is a potentially curative therapeutic approach for patients diagnosed with high-risk classic Hodgkin Lymphoma (cHL), a rare lymphoproliferative disorder. This study presents a comprehensive retrospective analysis of 273 patients with relapsed or refractory cHL referred to Taleghani Hospital in Tehran, Iran, over a 14-year period (2007–2021). The results indicated that 63 % of individuals receiving autologous-SCT achieved a complete response. However, approximately 4 % of the study population (10 patients) experienced treatment failure after autologous-SCT and proceeded to allogeneic-SCT (Group I). Additionally, in ten other cases, autologous-SCT was not feasible, and treatment was exclusively managed through allogeneic-SCT (Group II). Demographic and clinical characteristics, including gender, cHL subtype, history of radiotherapy, presence of bulky disease, and incidence of graft-versus-host disease (GVHD), were collected and analyzed to assess treatment outcomes. The overall survival (OS) was 42.1 months for Group I and 17.3 months for Group II. Although the overall complete response (CR) for the entire cohort was 45 %, the corresponding CR for Groups I and II were 60 and 30 %, respectively. In conclusion, allogenic-SCT appears to be a viable therapeutic strategy for at least 50 % of patients experiencing autologous-SCT failure. The efficacy of allogenic-SCT may be influenced by factors such as cHL subtype, and prior auto-SCT therapy. Notably, individuals in Group I who experienced graft-versus-host disease (GVHD) exhibited prolonged survival.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"90 ","pages":"Article 102228"},"PeriodicalIF":1.6,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143847995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recognition of different subsets of alloreactive T cells by activation-induced markers","authors":"Michiel G.H. Betjes,&nbsp;Mariska Klepper,&nbsp;Guido Smits,&nbsp;Elodie van der Valk,&nbsp;Amy C.J. van der List,&nbsp;Nicolle H.R. Litjens","doi":"10.1016/j.trim.2025.102227","DOIUrl":"10.1016/j.trim.2025.102227","url":null,"abstract":"<div><div>Alloreactive T-cells can be visualized using activation-induced markers (AIMs) including CD69, CD134, CD137 and CD154. Whether these AIMs recognize similar subsets of alloreactive T-cells is largely unknown. AIM-expressing alloreactive CD4+ T cells were analyzed in detail for phenotype by dissecting different T-cell subsets using antibodies directed to CCR7 and CD45RA. Moreover, detailed functional analysis was performed by determining proportions of cytokine producing cells within AIM-expressing CD4+ T cells using multiparameter flowcytometry. CD154 was predominantly expressed by naïve and central-memory alloreactive CD4+ T cells, CD134 by central-memory alloreactive CD4+ T cells and CD137 by CD4+ alloreactive memory T cells. Alloreactive CD8+ T cells could only be recognized by CD137 expression. The majority of alloreactive CD4+ T cells were single AIM-positive (72 %) and co-expression of all AIMs was infrequent. Polyclonal stimulation with anti-CD3/anti-CD28 resulted in a high frequency of CD4+ T cells co-expressing AIMs which was a dose-dependent phenomenon. Alloreactive memory CD4+ T cells expressing &gt;1 AIM showed the highest proportion of polyfunctional cells. Allogeneic stimulation of sorted naïve CD4+ T cells yielded a population of proliferating T cells, progressing to effector-memory T cells expressing &gt;1 AIM. In conclusion, different AIMs are preferentially expressed by different subsets of circulating alloreactive CD4+ T cells and expression of AIMs is determined by proliferation/differentiation and strength of the T cell receptor (TCR)-stimulation.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"90 ","pages":"Article 102227"},"PeriodicalIF":1.6,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143808310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}