{"doi":"10.1093/intimm/dxab108","title":"Memory-phenotype CD4+ T cells: a naturally arising T lymphocyte population possessing innate immune function","abstract":"In conventional adaptive immune responses, upon recognition of foreign antigens, naive CD4+ T lymphocytes are activated to differentiate into effector/memory cells. In addition, emerging evidence suggests that in the steady state, naive CD4+ T cells spontaneously proliferate in response to self-antigens to acquire a memory phenotype (MP) through homeostatic proliferation. This expansion is particularly profound in lymphopenic environments but also occurs in lymphoreplete, normal conditions. The 'MP T lymphocytes' generated in this manner are maintained by rapid proliferation in the periphery and they tonically differentiate into T-bet-expressing 'MP1' cells. Such MP1 CD4+ T lymphocytes can exert innate effector function, producing IFN-γ in response to IL-12 in the absence of antigen recognition, thereby contributing to host defense. In this review, we will discuss our current understanding of how MP T lymphocytes are generated and persist in steady-state conditions, their populational heterogeneity as well as the evidence for their effector function. We will also compare these properties with those of a similar population of innate memory cells previously identified in the CD8+ T lymphocyte lineage.","journal":"International Immunology","year":2021,"id":176934,"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":21,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9471,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":330710,"name":"Alan Sher","orcid":"0000-0001-7053-2895","position":1,"is_corresponding":false},{"id":506216,"name":"Takeshi Kawabe","orcid":"0000-0001-7173-4472","position":0,"is_corresponding":true}],"reference_count":79,"raw_metadata":null,"created_at":"2026-07-18T23:47:28.018172Z","pmid":"34897483","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":[]}