{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T13:09:55Z","timestamp":1791119395387,"version":"4.1.0"},"reference-count":0,"publisher":"National Academy of Sciences","issue":"19","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1990,10]]},"abstract":"<jats:p>Individuals infected by the human immunodeficiency virus type 1 (HIV-1) demonstrate progressive depletion and qualitative dysfunction of the helper T4 (CD4+) cell population. Mechanisms proposed for attrition of CD4+ T cells include direct cytopathicity of these mature cells following infection as well as infection of early T-lymphocyte progenitors. The latter mechanism could lead to failure to regenerate mature functioning CD4+ T cells. The present study determines the susceptibility of thymocytes at various stages of maturity to infection with HIV-1. Various normal thymocyte populations were inoculated with HIV-1, including unfractionated (UF), CD3- CD4- CD8- [\"triple negative\" (TN)], CD4+ CD8+ [\"double positive\" (DP)] thymocytes, and thymocyte populations obtained by limited dilution cloning. Cultures were studied for the presence of HIV-1 DNA by polymerase chain reaction in addition to examination for reverse transcriptase activity. We determined that transformed T-cell and thymocyte cell lines completely lacking CD4 were not susceptible to infection by HIV-1, whereas all of the following lines were: UF thymocytes (70-90% CD4hi+); DP thymocytes (99% CD4hi+); TN thymocytes (0% CD4hi+); and TCR alpha beta +, TCR gamma delta +, or CD16+ CD3- (natural killer) thymocyte clones expressing variable levels of CD4 and representing the progeny of TN thymocytes. [TCR alpha beta + and TCR gamma delta + refer to the chains of the T-cell antigen receptor (TCR), and CD4hi refers to a strong rightward shift (greater than 30 linear channels) of the CD4 curve on flow cytometric analysis compared with control.] Monoclonal antibodies (mAbs) to CD4 (T4a epitope) but not to CD3 (T3) were capable of blocking infection of mature and immature CD4hi+ thymocytes. Moreover, anti-CD4(T4a) mAbs also inhibited infection of CD4hi- TN thymocytes, indicating that these T-cell precursors--despite their apparent \"triple negativity\" (CD3- CD4hi- CD8-)--expressed sufficient CD4 molecules to become infected. Cell sorter analysis with a panel of CD4 mAbs demonstrated a mean shift of the mean fluorescence channel (MFC) with CD4 mAbs on TN thymocytes of 6 +\/- 4 MFC units. Thus, intrathymic T-cell precursors and their progeny representing many stages of T-cell ontogeny are susceptible to infection by HIV-1, including early TN thymocytes, which express very low levels of CD4. Infection of multiple stages and multiple subsets of the T-cell lineage in man, mediated via the CD4 molecule, may explain the inability of the T-cell pool to regenerate in the setting of progressive HIV infection.<\/jats:p>","DOI":"10.1073\/pnas.87.19.7727","type":"journal-article","created":{"date-parts":[[2006,5,31]],"date-time":"2006-05-31T07:27:44Z","timestamp":1149060464000},"page":"7727-7731","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":89,"title":["Evidence for susceptibility of intrathymic T-cell precursors and their progeny carrying T-cell antigen receptor phenotypes TCR alpha beta + and TCR gamma delta + to human immunodeficiency virus infection: a mechanism for CD4+ (T4) lymphocyte depletion."],"prefix":"10.1073","volume":"87","author":[{"given":"S M","family":"Schnittman","sequence":"first","affiliation":[{"name":"Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S M","family":"Denning","sequence":"additional","affiliation":[{"name":"Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J J","family":"Greenhouse","sequence":"additional","affiliation":[{"name":"Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J S","family":"Justement","sequence":"additional","affiliation":[{"name":"Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Baseler","sequence":"additional","affiliation":[{"name":"Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Kurtzberg","sequence":"additional","affiliation":[{"name":"Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B F","family":"Haynes","sequence":"additional","affiliation":[{"name":"Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A S","family":"Fauci","sequence":"additional","affiliation":[{"name":"Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1990,10]]},"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.87.19.7727","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T13:24:07Z","timestamp":1649856247000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.87.19.7727"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1990,10]]},"references-count":0,"journal-issue":{"issue":"19","published-print":{"date-parts":[[1990,10]]}},"alternative-id":["10.1073\/pnas.87.19.7727"],"URL":"https:\/\/doi.org\/10.1073\/pnas.87.19.7727","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[1990,10]]},"assertion":[{"value":"1990-10-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}