{"doi":"10.17615/jtc4-w930","title":"Antibody Binding to CD4 Induces Rac GTPase Activation and Alters T Cell Migration","abstract":"The use of nondepleting Ab specific for CD4 and CD8 is an effective strategy to tolerize CD4+ and CD8+ T cells in a tissue-specific manner. We reported that coreceptor therapy reverses diabetes in new onset NOD mice. A striking feature of coreceptor-induced remission is the purging of T cells from the pancreatic lymph nodes (PLN) and islets of NOD mice. Evidence indicates that Ab binding to the coreceptors promotes T cell egress from these tissues. The current study examined how coreceptor therapy affects the migration of CD4+ T cells residing in the PLN of NOD mice. αCD4 Ab treatment resulted in an increased frequency of PLN but not splenic CD4+ T cells that exhibited a polarized morphology consistent with a migratory phenotype. Furthermore, PLN CD4+ T cells isolated from αCD4 versus control Ab-treated animals displayed increased in vitro chemotaxis to chemoattractants such as sphingosine-1-phosphate and CXCL12. Notably, the latter was dependent on activation of the small Rho GTPases Rac1 and Rac2. Rac1 and Rac2 activation was increased in Ab-bound CD4+ T cells from the PLN but not the spleen, and knockdown of Rac expression blocked the heightened reactivity of Ab-bound PLN CD4+ T cells to CXCL12. Interestingly, Rac1 and Rac2 activation was independent of Rac guanine nucleotide exchange factors known to regulate T cell activity. Therefore, Ab binding to CD4 initiates a novel pathway that involves inflammation-dependent activation of Rac, and establishment of altered T cell migratory properties.","journal":"UNC Libraries","year":2020,"id":142418,"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":0.9535,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":284022,"name":"Rui Zhang","orcid":"0000-0002-6147-1573","position":1,"is_corresponding":false},{"id":392676,"name":"Keith Burridge","orcid":"0000-0002-2152-9670","position":2,"is_corresponding":false},{"id":272310,"name":"Matthew M. Clark","orcid":"0000-0003-3887-4419","position":3,"is_corresponding":false},{"id":303002,"name":"Y. Maurice Morillon","orcid":null,"position":4,"is_corresponding":false},{"id":608954,"name":"Bo Wang","orcid":"0000-0002-9196-6366","position":5,"is_corresponding":false},{"id":608955,"name":"Elizabeth C. Lessey-Morillon","orcid":"0000-0001-7885-6173","position":6,"is_corresponding":false},{"id":533176,"name":"Roland Tisch","orcid":"0000-0001-7751-7241","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:17:31.424593Z","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":[]}