{"doi":"10.1101/2022.05.21.492934","title":"Transplantation Elicits a Clonally Diverse CD8 <sup>+</sup> T Cell Response that is Comprised of Potent CD43 <sup>+</sup> Effectors","abstract":"SUMMARY CD8 + T cells mediate acute rejection of allografts, which threatens the long-term survival of transplanted organs. The factors that govern differentiation of graft-directed effector CD8 + T cells could lead to targeted approaches to limit acute rejection. Using MHC Class I tetramers, we found that allogeneic CD8 + T cells were present at an elevated precursor frequency in naïve mice, only modestly increased in number after grafting, and maintained high T cell receptor diversity throughout the immune response. While antigen-specific effector CD8 + T cells poorly express the canonical effector marker KLRG-1, expression of the activated glycoform of CD43 defined potent effectors after transplantation. Activated CD43 + effector T cells maintained high expression of ICOS in the presence of CTLA-4 Ig, and dual CTLA-4 Ig/anti-ICOS treatment prolonged graft survival. These data demonstrate that graft-specific CD8 + T cells have a distinct response profile relative to anti-pathogen CD8 + T cells, and that CD43 and ICOS are critical surface receptors that define potent effector CD8 + T cell populations that form after transplantation.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":308778,"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":0.9554,"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":997211,"name":"Melissa A. Kallarakal","orcid":"0009-0000-9948-3871","position":1,"is_corresponding":false},{"id":808762,"name":"Sahana Jayaraman","orcid":"0000-0003-3413-2530","position":2,"is_corresponding":false},{"id":997748,"name":"Francis I. Ibukun","orcid":null,"position":3,"is_corresponding":false},{"id":505684,"name":"Katherine P. Tong","orcid":null,"position":4,"is_corresponding":false},{"id":1003428,"name":"Linda D. Orzolek","orcid":null,"position":5,"is_corresponding":false},{"id":108428,"name":"H. Benjamin Larman","orcid":"0000-0001-7863-196X","position":6,"is_corresponding":false},{"id":504860,"name":"Scott M. Krummey","orcid":"0000-0002-7504-9162","position":7,"is_corresponding":false},{"id":1003972,"name":"Gregory Cohen","orcid":null,"position":0,"is_corresponding":true}],"reference_count":55,"raw_metadata":null,"created_at":"2026-07-19T00:33:07.132912Z","pmid":null,"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":[]}