{"doi":"10.3389/fimmu.2024.1343616","title":"Early allogeneic immune modulation after establishment of donor hematopoietic cell-induced mixed chimerism in a nonhuman primate kidney transplant model","abstract":"Background: Mixed lymphohematopoietic chimerism is a proven strategy for achieving operational transplant tolerance, though the underlying immunologic mechanisms are incompletely understood. Methods: A post-transplant, non-myeloablative, tomotherapy-based total lymphoid (TLI) irradiation protocol combined with anti-thymocyte globulin and T cell co-stimulatory blockade (belatacept) induction was applied to a 3-5 MHC antigen mismatched rhesus macaque kidney and hematopoietic cell transplant model. Mechanistic investigations of early (60 days post-transplant) allogeneic immune modulation induced by mixed chimerism were conducted. Results: mixed lymphocyte reaction (MLR) responses and donor-specific antibody production were suppressed in animals with mixed chimerism. PD-1 upregulation was observed among CD8+ T effector memory (CD28-CD95+) subsets in chimeric hosts only. PD-1 blockade in donor-specific functional assays augmented MLR and cytotoxic responses and was associated with increased intracellular granzyme B and extracellular IFN-γ production. Conclusions: These studies demonstrated that donor immune cell engraftment was associated with early immunomodulation via mechanisms of homeostatic expansion of Tregs and early PD-1 upregulation among CD8+ T effector memory cells. These responses may contribute to TLI-based mixed chimerism-induced allogenic tolerance.","journal":"Frontiers in Immunology","year":2024,"id":448236,"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":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9623,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":950466,"name":"Steven C. Kim","orcid":"0000-0001-8221-8043","position":1,"is_corresponding":false},{"id":1157966,"name":"John H. Fechner","orcid":"0000-0002-8220-7237","position":2,"is_corresponding":false},{"id":1267271,"name":"Jen Post","orcid":null,"position":3,"is_corresponding":false},{"id":484963,"name":"Jennifer Coonen","orcid":"0000-0001-5403-3412","position":4,"is_corresponding":false},{"id":484961,"name":"Peter J. Chlebeck","orcid":"0000-0003-1841-1652","position":5,"is_corresponding":false},{"id":1267272,"name":"Max Winslow","orcid":null,"position":6,"is_corresponding":false},{"id":1267273,"name":"Dennis Kobuzi","orcid":null,"position":7,"is_corresponding":false},{"id":259286,"name":"Samuel Strober","orcid":"0000-0002-1765-2326","position":8,"is_corresponding":false},{"id":351265,"name":"Dixon B. Kaufman","orcid":"0000-0003-3615-0994","position":9,"is_corresponding":false},{"id":963492,"name":"Christopher J. Little","orcid":"0000-0001-9723-2366","position":0,"is_corresponding":true}],"reference_count":65,"raw_metadata":null,"created_at":"2026-07-19T02:02:08.018689Z","pmid":"38318170","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":[]}