{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T02:38:03Z","timestamp":1791081483039,"version":"4.1.0"},"reference-count":0,"publisher":"Rockefeller University Press","issue":"5","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1988,11,1]]},"abstract":"<jats:p>A large number of CD4+ T cell clones, obtained from peripheral blood T lymphocytes by direct limiting dilution, allowed us to address the question whether functional heterogeneity exists within the human CD4+ T cell subset. Cytotoxic capacity of cloned T cells was analyzed with the use of anti-CD3 antibodies and target cells bearing FcR for murine IgG. 6 of 12 CD4+ clones obtained were able to lyse Daudi or P815 cells in the presence of anti-CD3 antibodies. The remaining six CD4+ T cell clones tested did not display anti-CD3-mediated cytotoxic activity and did not acquire this cytotoxic capacity during a culture period of 20 wk. In the absence of anti-CD3 mAb, no lytic activity against Daudi, P815, and K562 target cells was observed under normal culture conditions. Phenotypic analysis of these two distinct types of CD4+ T cells did not reveal differences with regard to reactivity with CDw29 (4B4) and CD45R (2H4) mAbs that have been described to recognize antigens associated with helper suppressor\/inducer (respectively) CD4+ cells. The CD4+ clones without anti-CD3-mediated cytotoxic activities (Th2) consistently showed a high expression level of CD28 antigens, whereas the cytotoxic clones (Th1) expressed low amounts of CD28. Th1 CD4+ clones did produce IL-2, IFN-gamma, and TNF-alpha\/beta, whereas the Th2 T cell clones produced minimal amounts of IL-2 and only low levels of INF-gamma and TNF-alpha\/beta in response to anti-CD3 mAbs and PMA. Although not all CD4+ clones did release IL-4, there was no correlation with cytotoxic activity. Moreover, as compared with the Th1 CD4+ clones, Th2 CD4+ T cell clones proliferated moderately in response to immobilized anti-CD3 mAbs. However, proliferation reached the level of the cytotoxic clones when anti-CD28 mABs were present during culture. Both CD4+ subsets provided help for B cell differentiation upon stimulation with anti-CD3 mAbs. Our data suggest that the human CD4+ subset, in analogy to the murine system, comprises two functionally distinct T cell subpopulations, both of which are able to exert helper activity for polyclonal B cell differentiation, but which differ in cytotoxic capacity, lymphokine production, and requirements for proliferation. A function for these two types of T cells in the immune response is discussed.<\/jats:p>","DOI":"10.1084\/jem.168.5.1659","type":"journal-article","created":{"date-parts":[[2004,6,24]],"date-time":"2004-06-24T07:56:10Z","timestamp":1088063770000},"page":"1659-1673","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":72,"title":["Clonal analysis of functionally distinct human CD4+ T cell subsets."],"prefix":"10.1084","volume":"168","author":[{"given":"F T","family":"Rotteveel","sequence":"first","affiliation":[{"name":"Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I","family":"Kokkelink","sequence":"additional","affiliation":[{"name":"Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R A","family":"van Lier","sequence":"additional","affiliation":[{"name":"Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B","family":"Kuenen","sequence":"additional","affiliation":[{"name":"Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Meager","sequence":"additional","affiliation":[{"name":"Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F","family":"Miedema","sequence":"additional","affiliation":[{"name":"Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C J","family":"Lucas","sequence":"additional","affiliation":[{"name":"Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[1988,11,1]]},"container-title":["The Journal of experimental medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/168\/5\/1659\/1669064\/1659.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/168\/5\/1659\/1669064\/1659.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,25]],"date-time":"2023-07-25T01:23:44Z","timestamp":1690248224000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jem\/article\/168\/5\/1659\/49943\/Clonal-analysis-of-functionally-distinct-human-CD4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1988,11,1]]},"references-count":0,"journal-issue":{"issue":"5","published-print":{"date-parts":[[1988,11,1]]}},"URL":"https:\/\/doi.org\/10.1084\/jem.168.5.1659","relation":{},"ISSN":["0022-1007","1540-9538"],"issn-type":[{"value":"0022-1007","type":"print"},{"value":"1540-9538","type":"electronic"}],"subject":[],"published":{"date-parts":[[1988,11,1]]}}}