{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T01:07:05Z","timestamp":1791248825837,"version":"4.1.0"},"reference-count":48,"publisher":"National Academy of Sciences","issue":"10","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2005,3,8]]},"abstract":"<jats:p>\n                    CD8\n                    <jats:sup>+<\/jats:sup>\n                    T lymphocytes play a major role in cellular-mediated immune responses to foreign antigen. We have previously demonstrated that costimulation of purified human CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells induces\n                    <jats:italic>de novo<\/jats:italic>\n                    expression of the CD4 molecule and that ligation of CD4 on this cell type modulates CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell activity\n                    <jats:italic>in vitro<\/jats:italic>\n                    . Herein, we investigate how the CD4 molecule expressed on murine CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells contributes to CD8\n                    <jats:sup>+<\/jats:sup>\n                    cell responses\n                    <jats:italic>in vivo<\/jats:italic>\n                    by employing adoptive transfer of CD8 cells from CD4 knockout mice into severe combined immunodeficient (SCID) recipients. Transfer of these cells into syngeneic SCID mice resulted in a decreased immune response to infection by lymphocytic choriomeningitis virus. These decreased responses occurred even in the presence of CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells, indicating that this was truly a CD8-cell defect. Similarly, transfer of CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells incapable of expressing CD4 into allogeneic SCID mice resulted in a decreased response to alloantigens compared with that of normal CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells. Therefore, CD4 expression on CD8 T lymphocytes modulates cytotoxic T lymphocyte function and is critical\n                    <jats:italic>in vivo<\/jats:italic>\n                    for optimal cell-mediated immunity to viral and alloantigens.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0406603102","type":"journal-article","created":{"date-parts":[[2005,2,24]],"date-time":"2005-02-24T20:31:51Z","timestamp":1109277111000},"page":"3794-3799","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":50,"title":["The CD4 molecule on CD8\n                    <sup>+<\/sup>\n                    T lymphocytes directly enhances the immune response to viral and cellular antigens"],"prefix":"10.1073","volume":"102","author":[{"given":"Scott G.","family":"Kitchen","sequence":"first","affiliation":[{"name":"Departments of Medicine and Microbiology, Immunology, and Molecular Genetics and UCLA AIDS Institute, David Geffen School of Medicine, University of California, Los Angeles, CA 90095; Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037; and Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason K.","family":"Whitmire","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Microbiology, Immunology, and Molecular Genetics and UCLA AIDS Institute, David Geffen School of Medicine, University of California, Los Angeles, CA 90095; Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037; and Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole R.","family":"Jones","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Microbiology, Immunology, and Molecular Genetics and UCLA AIDS Institute, David Geffen School of Medicine, University of California, Los Angeles, CA 90095; Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037; and Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoran","family":"Galic","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Microbiology, Immunology, and Molecular Genetics and UCLA AIDS Institute, David Geffen School of Medicine, University of California, Los Angeles, CA 90095; Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037; and Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina M. R.","family":"Kitchen","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Microbiology, Immunology, and Molecular Genetics and UCLA AIDS Institute, David Geffen School of Medicine, University of California, Los Angeles, CA 90095; Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037; and Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafi","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Microbiology, Immunology, and Molecular Genetics and UCLA AIDS Institute, David Geffen School of Medicine, University of California, Los Angeles, CA 90095; Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037; and Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerome A.","family":"Zack","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Microbiology, Immunology, and Molecular Genetics and UCLA AIDS Institute, David Geffen School of Medicine, University of California, Los Angeles, CA 90095; Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037; and Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2005,2,24]]},"reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni969"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-2427(99)00118-X"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1006\/clim.2000.4902"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.75.23.11555-11564.2001"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1006\/cimm.1993.1163"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/349533a0"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.73.9.7633-7640.1999"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-8749(02)00024-2"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0401500101"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2567.2001.01243.x"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.187.7.1139"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.72.11.9054-9060.1998"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.6.3111"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-5699(00)01629-7"},{"key":"e_1_3_2_15_2","first-page":"47","volume":"205","year":"1996","unstructured":"Ravichandran, K. S., Collins, T. L. & Burakoff, S. J. (1996) Curr. Top. Microbiol. Immunol. 205, 47-62.8575197","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V99.1.207"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/342559a0"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.160.2.521"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80470-7"},{"key":"e_1_3_2_20_2","doi-asserted-by":"crossref","first-page":"5543","DOI":"10.4049\/jimmunol.157.12.5543","volume":"157","year":"1996","unstructured":"van der Most, R. G., Sette, A., Oseroff, C., Alexander, J., Murali-Krishna, K., Lau, L. L., Southwood, S., Sidney, J., Chesnut, R. W., Matloubian, M. & Ahmed, R. (1996) J. Immunol. 157, 5543-5554.8955205","journal-title":"J. Immunol."},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.68.12.8056-8063.1994"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V84.8.2622.2622"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V96.1.195.013k51_195_202"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-81-10-2341"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/82712"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1369-5274(00)00199-5"},{"key":"e_1_3_2_27_2","doi-asserted-by":"crossref","first-page":"2456","DOI":"10.4049\/jimmunol.158.5.2456","volume":"158","year":"1997","unstructured":"Oyaizu, N., Adachi, Y., Hashimoto, F., McCloskey, T. W., Hosaka, N., Kayagaki, N., Yagita, H. & Pahwa, S. (1997) J. Immunol. 158, 2456-2463.9036997","journal-title":"J. Immunol."},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V84.10.3344.3344"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V89.4.1364"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.73.10.7972-7980.1999"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.102672999"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.169.1.327"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-1759(90)90256-U"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-10-3056"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V97.11.3484"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.65.2.736-742.1991"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.170.4.2053"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1082305"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/353180a0"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.70.2.1072-1079.1996"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01441"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1083317"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20031961"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.173.4.2494"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.10.5864"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni912"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.12.6833"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1038\/87720"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0406603102","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,2]],"date-time":"2023-05-02T06:19:44Z","timestamp":1683008384000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0406603102"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,2,24]]},"references-count":48,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2005,3,8]]}},"alternative-id":["10.1073\/pnas.0406603102"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0406603102","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,2,24]]},"assertion":[{"value":"2004-09-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2005-01-26","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2005-02-24","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}