{"doi":"10.1128/jvi.76.19.9981-9990.2002","title":"Decreased Levels of Recent Thymic Emigrants in Peripheral Blood of Simian Immunodeficiency Virus-Infected Macaques Correlate with Alterations within the Thymus","abstract":"<jats:title>ABSTRACT</jats:title><jats:p>The thymus is responsible for de novo production of CD4<jats:sup>+</jats:sup>and CD8<jats:sup>+</jats:sup>T cells and therefore is essential for T-cell renewal. The goal of this study was to assess the impact of simian immunodeficiency virus (SIV) infection on the production of T cells by the thymus. Levels of recent thymic emigrants within the peripheral blood were assessed through quantification of macaque T-cell receptor excision circles (TREC). Comparison of SIV-infected macaques (<jats:italic>n</jats:italic>= 15) to uninfected macaques (<jats:italic>n</jats:italic>= 23) revealed stable or increased TREC levels at 20 to 34 weeks postinfection. Further assessment of SIV-infected macaques (<jats:italic>n</jats:italic>= 4) determined that TREC levels decreased between 24 and 48 weeks postinfection. Through the assessment of longitudinal time points in three additional SIVmac239-infected macaques, the SIV infection was divided into two distinct phases. During phase 1 (16 to 30 weeks), TREC levels remained stable or increased within both the CD4 and CD8 T-cell populations. During phase 2 (after 16 to 30 weeks), TREC levels declined in both T-cell populations. As has been described for human immunodeficiency virus (HIV)-infected patients, this decline in TREC levels did at times correlate with an increased level of T-cell proliferation (Ki67<jats:sup>+</jats:sup>cells). However, not all TREC decreases could be attributed to increased T-cell proliferation. Further evidence for thymic dysfunction was observed directly in a SIVmac239-infected macaque that succumbed to simian AIDS at 65 weeks postinfection. The thymus of this macaque contained an increased number of memory/effector CD8<jats:sup>+</jats:sup>T cells and an increased level of apoptotic cells. In summary, reduced levels of TREC can be observed beginning at 16 to 30 weeks post-SIV infection and correlate with changes indicative of dysfunction within the thymic tissue. SIV infection of macaques will be a useful model system to elucidate the mechanisms responsible for the thymic dysfunction observed in HIV-infected patients.</jats:p>","journal":"Journal of Virology","year":2002,"id":635868,"datarank":0.5775221402565088,"base_score":3.8501476017100584,"endowment":3.8501476017100584,"self_citation_contribution":0.5775221402565088,"citation_network_contribution":0.0,"self_endowment_contribution":0.5775221402565088,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":46,"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":228707,"name":"Jeffrey M. Milush","orcid":"0000-0002-0773-6411","position":1,"is_corresponding":false},{"id":1649939,"name":"Felecia Ware","orcid":null,"position":2,"is_corresponding":false},{"id":1649940,"name":"Aneta Wozniakowski","orcid":null,"position":3,"is_corresponding":false},{"id":1649942,"name":"Lisa Montgomery","orcid":null,"position":4,"is_corresponding":false},{"id":1551290,"name":"Harold M. McClure","orcid":null,"position":5,"is_corresponding":false},{"id":819979,"name":"Andrew A. Lackner","orcid":"0000-0003-2162-1079","position":6,"is_corresponding":false},{"id":1649945,"name":"Marta Marthas","orcid":null,"position":7,"is_corresponding":false},{"id":1649947,"name":"Vanessa Hirsch","orcid":null,"position":8,"is_corresponding":false},{"id":551177,"name":"R. Paul Johnson","orcid":null,"position":9,"is_corresponding":false},{"id":277153,"name":"Daniel C. Douek","orcid":"0000-0001-5575-8634","position":10,"is_corresponding":false},{"id":290824,"name":"Richard A. Koup","orcid":"0000-0002-3090-7282","position":11,"is_corresponding":false},{"id":445039,"name":"Donald L. Sodora","orcid":"0000-0002-8927-052X","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Decreased Levels of Recent Thymic Emigrants in Peripheral Blood of Simian Immunodeficiency Virus-Infected Macaques Correlate with Alterations within the Thymus","abstract":"<jats:title>ABSTRACT</jats:title><jats:p>The thymus is responsible for de novo production of CD4<jats:sup>+</jats:sup>and CD8<jats:sup>+</jats:sup>T cells and therefore is essential for T-cell renewal. The goal of this study was to assess the impact of simian immunodeficiency virus (SIV) infection on the production of T cells by the thymus. Levels of recent thymic emigrants within the peripheral blood were assessed through quantification of macaque T-cell receptor excision circles (TREC). Comparison of SIV-infected macaques (<jats:italic>n</jats:italic>= 15) to uninfected macaques (<jats:italic>n</jats:italic>= 23) revealed stable or increased TREC levels at 20 to 34 weeks postinfection. Further assessment of SIV-infected macaques (<jats:italic>n</jats:italic>= 4) determined that TREC levels decreased between 24 and 48 weeks postinfection. Through the assessment of longitudinal time points in three additional SIVmac239-infected macaques, the SIV infection was divided into two distinct phases. During phase 1 (16 to 30 weeks), TREC levels remained stable or increased within both the CD4 and CD8 T-cell populations. During phase 2 (after 16 to 30 weeks), TREC levels declined in both T-cell populations. As has been described for human immunodeficiency virus (HIV)-infected patients, this decline in TREC levels did at times correlate with an increased level of T-cell proliferation (Ki67<jats:sup>+</jats:sup>cells). However, not all TREC decreases could be attributed to increased T-cell proliferation. Further evidence for thymic dysfunction was observed directly in a SIVmac239-infected macaque that succumbed to simian AIDS at 65 weeks postinfection. The thymus of this macaque contained an increased number of memory/effector CD8<jats:sup>+</jats:sup>T cells and an increased level of apoptotic cells. In summary, reduced levels of TREC can be observed beginning at 16 to 30 weeks post-SIV infection and correlate with changes indicative of dysfunction within the thymic tissue. SIV infection of macaques will be a useful model system to elucidate the mechanisms responsible for the thymic dysfunction observed in HIV-infected patients.</jats:p>","is_dataset_classified":null,"base_score":3.8501476017100584,"endowment":3.8501476017100584,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"12208974","pmcid":"PMC136511","openalex_id":"https://openalex.org/W2018306895","authors":[],"funders":[{"funder_name":"NCRR NIH HHS","grant_id":"P51 RR000168","title":null},{"funder_name":"NCRR NIH HHS","grant_id":"RR00168","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"AI35522","title":null},{"funder_name":"NCRR NIH HHS","grant_id":"P51 RR000169","title":null},{"funder_name":"NIDCR NIH HHS","grant_id":"R01 DE012926","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"R37 AI035522","title":null},{"funder_name":"NCRR NIH HHS","grant_id":"K26 RR000168","title":null},{"funder_name":"NIDCR NIH HHS","grant_id":"DE12926","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"R01 AI035522","title":null},{"funder_name":"NCRR NIH HHS","grant_id":"RR00169","title":null}],"total_grants":10,"fwci":1.6018,"citation_percentile":0.80923521,"influential_citations":0,"citation_trend":[{"year":2012,"count":2},{"year":2013,"count":3},{"year":2014,"count":1},{"year":2021,"count":2},{"year":2024,"count":1},{"year":2025,"count":2},{"year":2026,"count":1}],"oa_status":"green","license":"https://journals.asm.org/non-commercial-tdm-license","oa_locations":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/136511","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/136511","host_type":"repository"},{"url":"https://journals.asm.org/doi/pdf/10.1128/JVI.76.19.9981-9990.2002","host_type":"publisher"},{"url":"https://doi.org/10.1128/jvi.76.19.9981-9990.2002","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/12208974","host_type":"repository"}],"fields_of_study":["HIV Research and Treatment","HIV/AIDS Research and Interventions","Immune Cell Function and Interaction","Animals","Apoptosis","CD4 Lymphocyte Count","Cell Movement","Gene Rearrangement, T-Lymphocyte","In Situ Nick-End Labeling","Macaca mulatta","Simian Acquired Immunodeficiency Syndrome","Thymus Gland"],"mesh_terms":["Animals","Cell Movement","Macaca mulatta","Thymus Gland","Gene Rearrangement, T-Lymphocyte","Simian Acquired Immunodeficiency Syndrome","Apoptosis","CD4 Lymphocyte Count","In Situ Nick-End Labeling"],"keywords":["Simian immunodeficiency virus","Biology","Macaque","Rhesus macaque","CD8","Virology","T cell","Immunology","Immunodeficiency","Virus","Lentivirus","Viral disease","Immune system"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-06T15:43:47.004347Z","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":[]}