{"doi":"10.4049/jimmunol.156.11.4114","title":"Adoptively transferred CD4+ lymphocytes from CD8 -/- mice are sufficient to mediate the rejection of MHC class II or class I disparate skin grafts","abstract":"<jats:title>Abstract</jats:title>\n                  <jats:p>Recent studies revealed that CD4+ cells initiate allograft rejection through direct recognition of allogeneic MHC class II Ags and indirect recognition of MHC peptides processed by self APCs. Both pathways were shown to help CD8+ cells that eventually lysed allogeneic MHC class I-presenting targets. There was little evidence, however, that CD4+ cells are sufficient for graft rejection. We studied skin graft rejection by CD8-deficient (CD8 -/-) mice. We showed that BALB/cJ(H-2d) CD8 -/- mice could reject allogeneic skin from C57BL/6J(H-2b) mice deficient in MHC class I or in MHC class II Ags. To understand the role of CD4+ cells in this process, we isolated them from CD8 -/- mice and transferred them to BALB/cJ nude mice that had been grafted with allogeneic skin (H-2b) from animals deficient in MHC class I or MHC class II. Nude mice injected with CD4+ cells rejected MHC class II and, albeit more slowly, MHC class I disparate skins. We showed in vitro evidence that CD4+ cells were not cytotoxic toward MHC class I or MHC class II disparate targets and that they recognized MHC class I allogeneic targets through indirect recognition. CD4+ cells produced Th1 cytokines, but not IL-4, following stimulation with allogeneic cells. Furthermore, intragraft TNF-α was elevated in skin grafted onto nude mice reconstituted with CD4+ cells compared with nonreconstituted mice. This suggests that MHC class II- or MHC class I-guided CD4+ cells alone are sufficient to induce rejection by the generation of cytokine-induced lesions.</jats:p>","journal":"The Journal of Immunology","year":1996,"id":594179,"datarank":0.6456097639806255,"base_score":4.304065093204169,"endowment":4.304065093204169,"self_citation_contribution":0.6456097639806255,"citation_network_contribution":0.0,"self_endowment_contribution":0.6456097639806255,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":73,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1520913,"name":"E Chmouzis","orcid":null,"position":1,"is_corresponding":false},{"id":1520916,"name":"K Ngo","orcid":null,"position":2,"is_corresponding":false},{"id":1520917,"name":"W P Fung-Leung","orcid":null,"position":3,"is_corresponding":false},{"id":1520910,"name":"A H Dalloul","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Adoptively transferred CD4+ lymphocytes from CD8 -/- mice are sufficient to mediate the rejection of MHC class II or class I disparate skin grafts","abstract":"<jats:title>Abstract</jats:title>\n                  <jats:p>Recent studies revealed that CD4+ cells initiate allograft rejection through direct recognition of allogeneic MHC class II Ags and indirect recognition of MHC peptides processed by self APCs. Both pathways were shown to help CD8+ cells that eventually lysed allogeneic MHC class I-presenting targets. There was little evidence, however, that CD4+ cells are sufficient for graft rejection. We studied skin graft rejection by CD8-deficient (CD8 -/-) mice. We showed that BALB/cJ(H-2d) CD8 -/- mice could reject allogeneic skin from C57BL/6J(H-2b) mice deficient in MHC class I or in MHC class II Ags. To understand the role of CD4+ cells in this process, we isolated them from CD8 -/- mice and transferred them to BALB/cJ nude mice that had been grafted with allogeneic skin (H-2b) from animals deficient in MHC class I or MHC class II. Nude mice injected with CD4+ cells rejected MHC class II and, albeit more slowly, MHC class I disparate skins. We showed in vitro evidence that CD4+ cells were not cytotoxic toward MHC class I or MHC class II disparate targets and that they recognized MHC class I allogeneic targets through indirect recognition. CD4+ cells produced Th1 cytokines, but not IL-4, following stimulation with allogeneic cells. Furthermore, intragraft TNF-α was elevated in skin grafted onto nude mice reconstituted with CD4+ cells compared with nonreconstituted mice. This suggests that MHC class II- or MHC class I-guided CD4+ cells alone are sufficient to induce rejection by the generation of cytokine-induced lesions.</jats:p>","is_dataset_classified":null,"base_score":4.304065093204169,"endowment":4.304065093204169,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"8666777","pmcid":null,"openalex_id":"https://openalex.org/W1562706914","authors":[],"funders":[],"total_grants":0,"fwci":2.4647,"citation_percentile":0.89637142,"influential_citations":0,"citation_trend":[{"year":2012,"count":2},{"year":2013,"count":2},{"year":2014,"count":3},{"year":2015,"count":1},{"year":2020,"count":1},{"year":2021,"count":2},{"year":2022,"count":2}],"oa_status":"closed","license":"https://academic.oup.com/pages/standard-publication-reuse-rights","oa_locations":[{"url":"https://academic.oup.com/jimmunol/article-pdf/156/11/4114/62363190/8666777.pdf","host_type":"publisher"},{"url":"https://doi.org/10.4049/jimmunol.156.11.4114","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/8666777","host_type":"repository"}],"fields_of_study":["Immunotherapy and Immune Responses","T-cell and B-cell Immunology","Cell Adhesion Molecules Research"],"mesh_terms":["Animals","Histocompatibility Antigens Class II","Cytotoxicity, Immunologic","Graft Rejection","Male","Mice, Inbred BALB C","Mice, Inbred C57BL","Mice, Nude","Models, Biological","Histocompatibility Antigens Class I","CD4-Positive T-Lymphocytes","Skin Transplantation","Cytokines","Immunotherapy, Adoptive","CD8 Antigens","Mice","In Vitro Techniques"],"keywords":["CD8","MHC class I","MHC class II","CD1","Major histocompatibility complex","Cytotoxic T cell","Immunology","MHC restriction","Biology","Immune system","In vitro","Interleukin 21","Genetics"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-27T13:48:05.411340Z","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":[]}