{"doi":"10.1167/iovs.65.1.40","title":"Effector T Cells Promote Fibrosis in Corneal Transplantation Failure","abstract":"Purpose: To evaluate whether fibrosis contributes to corneal transplant failure and to determine whether effector CD4+ T cells, the key immune cells in corneal transplant rejection, play a direct role in fibrosis formation. Methods: Allogeneic corneal transplantation was performed in mice. Graft opacity was evaluated by slit-lamp biomicroscopy, and fibrosis was assessed by in vivo confocal microscopy. Expression of alpha-smooth muscle actin (α-SMA) in both accepted and failed grafts was assessed by real-time PCR and immunohistochemistry. Frequencies of graft-infiltrating CD4+ T cells, neutrophils, and macrophages were assessed using flow cytometry. In vitro, MK/T-1 corneal fibroblasts were co-cultured with activated CD4+CD25- effector T cells isolated from corneal transplant recipient mice, and α-SMA expression was quantified by real-time PCR and ELISA. Neutralizing antibody was used to evaluate the role of interferon gamma (IFN-γ) in promoting α-SMA expression. Results: The majority of failed grafts demonstrated clinical signs of fibrosis which became most evident at week 6 after corneal transplantation. Failed grafts showed higher expression of α-SMA as compared to accepted grafts. Flow cytometry analysis showed a significant increase in CD4+ T cells in failed grafts compared to accepted grafts. Co-culture of activated CD4+CD25- effector T cells with corneal fibroblasts led to an increase in α-SMA expression by fibroblasts. Inhibition of IFN-γ in culture significantly suppressed this increase in α-SMA expression as compared to immunoglobulin G control. Conclusions: Fibrosis contributes to graft opacity in corneal transplant failure and is mediated at least in part by effector CD4+ T cells via IFN-γ.","journal":"Investigative Ophthalmology & Visual Science","year":2024,"id":457080,"datarank":0.26876392038420827,"base_score":1.791759469228055,"endowment":1.791759469228055,"self_citation_contribution":0.26876392038420827,"citation_network_contribution":0.0,"self_endowment_contribution":0.26876392038420827,"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":0.9584,"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":450681,"name":"Sharad K. Mittal","orcid":null,"position":1,"is_corresponding":false},{"id":1118404,"name":"Seok-Joo Lee","orcid":"0009-0003-7317-2583","position":2,"is_corresponding":false},{"id":1282820,"name":"Antonio Esquivel Herrera","orcid":null,"position":3,"is_corresponding":false},{"id":1282821,"name":"Mark Krauthammer","orcid":null,"position":4,"is_corresponding":false},{"id":474425,"name":"Elsayed Elbasiony","orcid":null,"position":5,"is_corresponding":false},{"id":332330,"name":"Tomás Blanco","orcid":"0000-0002-6829-117X","position":6,"is_corresponding":false},{"id":723185,"name":"Hamid Alemi","orcid":"0000-0001-8516-9574","position":7,"is_corresponding":false},{"id":732694,"name":"Hayate Nakagawa","orcid":"0000-0003-2831-3570","position":8,"is_corresponding":false},{"id":393255,"name":"Sunil K. Chauhan","orcid":"0000-0003-4938-6023","position":9,"is_corresponding":false},{"id":230209,"name":"Reza Dana","orcid":"0000-0002-5732-5100","position":10,"is_corresponding":false},{"id":400621,"name":"Thomas H. Dohlman","orcid":"0000-0002-3818-4541","position":11,"is_corresponding":false},{"id":660057,"name":"Shudan Wang","orcid":"0000-0002-9292-0992","position":0,"is_corresponding":true}],"reference_count":44,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:03:37.136946Z","pmid":"38261311","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":[]}