{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T02:12:01Z","timestamp":1792807921427,"version":"4.5.0"},"reference-count":38,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2003,4,1]],"date-time":"2003-04-01T00:00:00Z","timestamp":1049155200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2003,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Chemokines induce the directional migration of targeted populations of leukocytes during periods of inflammation. Moreover, these molecules also regulate T-cell activation and differentiation following antigenic stimulation. In the present study, the contributions of the CC chemokine ligand 3 (CCL3) to the differentiation and migration of effector T cells in response to viral infection of the central nervous system (CNS) were analyzed. CCL3<jats:sup>\u2212\/\u2212<\/jats:sup>mice infected with mouse hepatitis virus exhibited a significant reduction of virus-specific CD8<jats:sup>+<\/jats:sup>T cells within the CNS, correlating with delayed viral clearance. Decreased infiltration of CD8<jats:sup>+<\/jats:sup>T cells into infected CCL3<jats:sup>\u2212\/\u2212<\/jats:sup>mice was associated with enhanced accumulation of primed CD8<jats:sup>+<\/jats:sup>T cells in cervical lymph nodes. Although virus-specific CD8<jats:sup>+<\/jats:sup>T cells from CCL3<jats:sup>\u2212\/\u2212<\/jats:sup>mice were CD44<jats:sup>high<\/jats:sup>, they remained CD62L<jats:sup>high<\/jats:sup>and CD25<jats:sup>low<\/jats:sup>, retained CCR7 expression, and contained limited transcripts of the proinflammatory chemokine receptors CCR5 and CXCR3 compared with virus-specific CD8<jats:sup>+<\/jats:sup>T cells from CCL3<jats:sup>+\/+<\/jats:sup>mice. Furthermore, the absence of CCL3 impaired the cytokine production and cytolytic activity of CD8<jats:sup>+<\/jats:sup>T cells. In addition, macrophage accumulation within the CNS was significantly decreased in infected CCL3<jats:sup>\u2212\/\u2212<\/jats:sup>mice, correlating with reduced demyelination. These results suggest that CCL3 not only mediates macrophage chemotaxis but also significantly enhances differentiation of primed CD8<jats:sup>+<\/jats:sup>T cells into effector cells and their release into circulation, thus potentiating effective migration to the site of infection.<\/jats:p>","DOI":"10.1128\/jvi.77.7.4004-4014.2003","type":"journal-article","created":{"date-parts":[[2003,3,12]],"date-time":"2003-03-12T18:46:25Z","timestamp":1047494785000},"page":"4004-4014","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":112,"title":["CC Chemokine Ligand 3 (CCL3) Regulates CD8<sup>+<\/sup>-T-Cell Effector Function and Migration following Viral Infection"],"prefix":"10.1128","volume":"77","author":[{"given":"Matthew J.","family":"Trifilo","sequence":"first","affiliation":[{"name":"Department of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, California 92697-3900"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelia C.","family":"Bergmann","sequence":"additional","affiliation":[{"name":"Departments of Neurology and Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California 90033"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William A.","family":"Kuziel","sequence":"additional","affiliation":[{"name":"Section of Molecular Genetics and Microbiology and Institute for Cellular and Molecular Biology, University of Texas, Austin, Austin, Texas 78712"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas E.","family":"Lane","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, California 92697-3900"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-2776(08)60756-7"},{"key":"e_1_3_2_3_2","doi-asserted-by":"crossref","first-page":"3245","DOI":"10.4049\/jimmunol.152.7.3245","volume":"152","year":"1994","unstructured":"Ando, K., L. G. Guidotti, S. Wirth, T. Ishikawa, G. Missale, T. Moriyama, R. D. Schreiber, H. J. Schlicht, S. Huang, and F. V. Chisari. 1994. Class I-restricted cytotoxic T lymphocytes are directly cytopathic for their target cells in vivo. J. Immunol. 152 : 3245-3253.","journal-title":"J. Immunol."},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.164.1.144"},{"key":"e_1_3_2_5_2","doi-asserted-by":"crossref","first-page":"3379","DOI":"10.4049\/jimmunol.163.6.3379","volume":"163","year":"1999","unstructured":"Bergmann, C. C., J. D. Altman, D. Hinton, and S. A. Stohlman. 1999. Inverted immunodominance and impaired cytolytic function of CD8+ T cells during viral persistence in the central nervous system. J. Immunol. 163 : 3379-3387.","journal-title":"J. Immunol."},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/0952-7915(94)90137-6"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.8.4585"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7667639"},{"key":"e_1_3_2_9_2","doi-asserted-by":"crossref","first-page":"5690","DOI":"10.4049\/jimmunol.155.12.5690","volume":"155","year":"1995","unstructured":"Cousens, L. P., J. S. Orange, and C. A. Biron. 1995. Endogenous IL-2 contributes to T cell expansion and IFN-\u03b3 production during lymphocytic choriomeningitis virus infection. J. Immunol. 155 : 5690-5699.","journal-title":"J. Immunol."},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.5.2677"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.146.2.468"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.2001.1050"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.75.2.878-890.2001"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/1521-4141(200011)30:11<3207::AID-IMMU3207>3.0.CO;2-L"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.3109\/13550289609146902"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/jlb.62.5.681"},{"key":"e_1_3_2_17_2","doi-asserted-by":"crossref","first-page":"4129","DOI":"10.4049\/jimmunol.158.9.4129","volume":"158","year":"1997","unstructured":"Karpus, W. J., N. W. Lukacs, K. J. Kennedy, W. S. Smith, S. D. Hurst, and T. A. Barrett. 1997. Differential CC chemokine-induced enhancement of T helper cell cytokine production. J. Immunol. 158 : 4129-4136.","journal-title":"J. Immunol."},{"key":"e_1_3_2_18_2","doi-asserted-by":"crossref","first-page":"2316","DOI":"10.4049\/jimmunol.150.6.2316","volume":"150","year":"1993","unstructured":"Kundig, T. M., H. Hengartner, and R. M. Zinkernagel. 1993. T cell-dependent IFN-\u03b3 exerts an antiviral effect in the central nervous system but not in peripheral solid organs. J. Immunol. 150 : 2316-2321.","journal-title":"J. Immunol."},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.74.3.1415-1424.2000"},{"key":"e_1_3_2_20_2","doi-asserted-by":"crossref","first-page":"970","DOI":"10.4049\/jimmunol.160.2.970","volume":"160","year":"1998","unstructured":"Lane, T. E., V. C. Asensio, N. Yu, A. D. Paoletti, I. L. Campbell, and M. J. Buchmeier. 1998. Dynamic regulation of \u03b1- and \u03b2-chemokine expression in the central nervous system during mouse hepatitis virus-induced demyelinating disease. J. Immunol. 160 : 970-978.","journal-title":"J. Immunol."},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.290.5489.92"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.71.1.383-391.1997"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.69.10.6364-6369.2001"},{"key":"e_1_3_2_24_2","first-page":"2327","volume":"165","year":"2001","unstructured":"Liu, M. T., B. P. Chen, P. Oertel, M. J. Buchmeier, D. Armstrong, T. A. Hamilton, and T. E. Lane. 2001. Neutralization of the chemokine CXCL10 reduces inflammatory cell invasion and demyelination and improves neurologic function in a viral model of multiple sclerosis. J. Immunol. 165 : 2327-2330.","journal-title":"J. Immunol."},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.3.1790"},{"key":"e_1_3_2_26_2","first-page":"1861","volume":"150","year":"1997","unstructured":"Lukacs, N. W., S. W. Chensue, W. J. Karpus, P. Lincoln, C. Keefer, R. M. Strieter, and S. L. Kunkel. 1997. C-C chemokines differentially alter interleukin-4 production from lymphocytes. Am. J. Pathol. 150 : 1861-1868.","journal-title":"Am. J. Pathol."},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.3.1675"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI13296"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.2.962"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.181845"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.11.6429"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1997.8613"},{"key":"e_1_3_2_33_2","doi-asserted-by":"crossref","first-page":"1641","DOI":"10.4049\/jimmunol.162.3.1641","volume":"162","year":"1999","unstructured":"Parra, B., D. R. Hinton, N. W. Marten, C. C. Bergmann, M. T. Lin, C. S. Yang, and S. A. Stohlman. 1999. IFN-\u03b3 is required for viral clearance from central nervous system oligodendroglia. J. Immunol. 162 : 1641-1647.","journal-title":"J. Immunol."},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1521-4141(199911)29:11<3562::AID-IMMU3562>3.0.CO;2-R"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1521-4141(199906)29:06<2037::AID-IMMU2037>3.0.CO;2-V"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.18.1.593"},{"key":"e_1_3_2_37_2","doi-asserted-by":"crossref","first-page":"5007","DOI":"10.4049\/jimmunol.160.10.5007","volume":"160","year":"1998","unstructured":"Su, H. C., L. P. Cousens, L. D. Fast, M. K. Slifka, R. D. Bungiro, R. Ahmed, and C. A. Biron. 1998. CD4+ and CD8+ T cell interactions in IFN-\u03b3 and IL-4 responses to viral infections: requirements for IL-2. J. Immunol. 160 : 5007-5017.","journal-title":"J. Immunol."},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.23.10854"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.4.2278"}],"container-title":["Journal of Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.77.7.4004-4014.2003","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.77.7.4004-4014.2003","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,25]],"date-time":"2023-04-25T22:29:46Z","timestamp":1682461786000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/JVI.77.7.4004-4014.2003"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,4]]},"references-count":38,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2003,4]]}},"alternative-id":["10.1128\/JVI.77.7.4004-4014.2003"],"URL":"https:\/\/doi.org\/10.1128\/jvi.77.7.4004-4014.2003","relation":{},"ISSN":["0022-538X","1098-5514"],"issn-type":[{"value":"0022-538X","type":"print"},{"value":"1098-5514","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,4]]},"assertion":[{"value":"2002-06-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2002-12-31","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2003-04-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}