{"doi":"10.1016/j.ekir.2022.11.005","title":"Walking the Line Between Antidonor and Antiviral Immunity: A Potential Role for Belatacept","abstract":"Belatacept, a selective T-cell costimulation blocker, was introduced as a promising change from the nephrotoxic and metabolic side effects of calcineurin (CNI) based maintenance immunosuppression. Seven-year follow up of the belatacept-based immunosuppression regimens versus cyclosporine in renal transplant recipients (BENEFIT study) trial showed superior patient and graft survival along with higher mean estimated glomerular filtration rate with the use of belatacept as compared to cyclosporine.1Vincenti F. Rostaing L. Grinyo J. et al.Belatacept and long-term outcomes in kidney transplantation.N Engl J Med. 2016; 374: 333-343https://doi.org/10.1056/NEJMoa1506027Crossref PubMed Scopus (464) Google Scholar However, following its Food and Drug Administration approval in 2011, reportedly only 3% of transplant centers in the United States use belatacept as de novo or first line immunosuppression,2Karadkhele G. Duneton C. Garro R. et al.Temporal trends and current use of de novo Belatacept in kidney transplant recipients in the United States.Clin Transpl. 2022; 36e14531https://doi.org/10.1111/ctr.14531Crossref Scopus (7) Google Scholar although a larger proportion of patients may likely convert to belatacept from CNI in later months posttransplantation. Logistic barriers to regular intravenous administration, the increased rate of acute cellular rejection, and increased risk of opportunistic infections are the major barriers to its widespread adoption. A study by Schaenmen et al.3Schaenman J. Rossetti M. Pickering H. et al.Preservation of antiviral immunologic efficacy without alloimmunity after switch to Belatacept in CNI-intolerant patients.Kidney Int Rep. 2023; 8: 126-140Abstract Full Text Full Text PDF Scopus (1) Google Scholar published in this issue of KI Reports attempts to investigate the latter 2 issues in a prospective transplant cohort by assaying peripheral blood mononuclear cells (PBMCs) to study the immunologic impact of switching to belatacept maintenance immunosuppression. Specifically, the authors here investigated belatacept’s impact on T-cell phenotype in the context of donor-specific immunity (alloimmunity) and antiviral immunity. They studied 19 first time kidney transplant recipients with CNI toxicities (renal or others) who were switched to belatacept within 3 months of transplant and followed-up with for at least 6 months. At baseline and follow-up, the authors used a multiparameter panel to gate CD4+ and CD8+ T-cell populations for maturation subtypes i.e., naïve (CCR7+/CD45RA+), effector memory (CCR7+/CD45RA−) and terminally differentiated effector memory (CCR7−/CD45RA+ i.e., terminally differentiated effector memory) cells. In addition, exhaustion, senescence, and activation subsets were evaluated using the surface markers KLRG1, CD57, CD38, CD28, and PD-1. A 1-way mixed lymphocyte reaction (MLR), where inactivated donor cells were incubated with recipient PBMCs for 15 hours was used to study alloimmunity. To evaluate the impact on antiviral immunity, isolated PBMCs were incubated overnight with peptide pools representing cytomegalovirus (CMV) or Epstein-Barr virus (EBV) antigens, and surface markers and intracellular cytokine staining of responder T cells were assayed. Donor-specific antibody was measured in sera. All clinical and flow parameters were then compared to age-matched and transplant-matched controls on CNI therapy, as well as within-group analyses of slope using serial time points. Clinically, the authors identified no significant differences in rates of acute rejection, or infectious complications between study groups. In serial analyses, the authors report a consistent trend of reduced naïve T-cell- with increased terminally differentiated effector memory proportions with time from transplantation, regardless of belatacept or CNI. In donor-specific MLRs, the proportions of single-cytokine or double-cytokine (interferon gamma/tumor necrosis factor alfa) positive T cells were also similar betw","journal":"Kidney International Reports","year":2022,"id":313145,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9545,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":945184,"name":"John Pell","orcid":"0009-0000-9641-2445","position":1,"is_corresponding":false},{"id":385517,"name":"Madhav C. Menon","orcid":"0000-0002-9567-4299","position":2,"is_corresponding":false},{"id":1011409,"name":"Deepthi Gunasekaran","orcid":"0009-0003-8423-9317","position":0,"is_corresponding":true}],"reference_count":9,"raw_metadata":null,"created_at":"2026-07-19T00:33:44.454239Z","pmid":"36644356","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}