{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T16:48:33Z","timestamp":1790700513294,"version":"4.1.0"},"reference-count":50,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2010,12,1]],"date-time":"2010-12-01T00:00:00Z","timestamp":1291161600000},"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":["Infect Immun"],"published-print":{"date-parts":[[2010,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Infections caused by<jats:italic>Streptococcus pneumoniae<\/jats:italic>are major causes of morbidity and mortality, which are in part mediated by immune cell-dependent mechanisms. Yet, the specific contributions of individual cell types to immunopathology are only partially understood. T cells are well characterized with respect to their function in protective humoral immune responses; however, their roles during early stages of infection and invasive pneumococcal disease (IPD) are less well defined. Using a mouse model of pneumococcal sepsis, we found that CD4<jats:sup>+<\/jats:sup>T cells were recruited to the lung as early as 12 h after intranasal infection. Recruitment was accompanied by upregulation of CD69 and B7-H1, reflecting T-cell activation. Unexpectedly, major histocompatibility complex (MHC) class II-deficient mice, which lack CD4<jats:sup>+<\/jats:sup>T cells, displayed an increased survival despite comparable bacterial titers in the blood, spleen, and lung. The higher survival correlated with a lower cytokine and chemokine response upon<jats:italic>S. pneumoniae<\/jats:italic>challenge in MHC class II-deficient mice, suggesting that inflammation may contribute to the mortality of IPD. Comparable to the case for MHC class II-deficient mice, antibody-mediated depletion of CD4<jats:sup>+<\/jats:sup>T cells and drug-induced inhibition of T-cell function with cyclosporine, or interference with T-cell activation using CTLA4-immunoglobulin (Abatacept), led to significant increases in survival during IPD. Our results reveal an important and adverse role of CD4<jats:sup>+<\/jats:sup>T cells in the pathogenesis of IPD and suggest that modulation of T-cell activation during early phases of<jats:italic>S. pneumoniae<\/jats:italic>invasive infection may provide a therapeutic option.<\/jats:p>","DOI":"10.1128\/iai.00431-10","type":"journal-article","created":{"date-parts":[[2010,9,21]],"date-time":"2010-09-21T04:10:41Z","timestamp":1285042241000},"page":"5287-5294","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":33,"title":["Inhibition of T Cells Provides Protection against Early Invasive Pneumococcal Disease"],"prefix":"10.1128","volume":"78","author":[{"given":"Kim","family":"LeMessurier","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Ha\u0308cker","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elaine","family":"Tuomanen","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa","family":"Redecke","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/mr.59.4.591-603.1995"},{"key":"e_1_3_2_3_2","first-page":"35","volume":"18","year":"1986","unstructured":"Austrian, R. 1986. Some aspects of the pneumococcal carrier state. J. Antimicrob. Chemother.18(Suppl. A):35-45.","journal-title":"J. Antimicrob. Chemother."},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00773-07"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.66.3.912-922.1998"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.22750"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.177.6.1699"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1097\/INF.0b013e318124a494"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2009.02.093"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1136\/thx.54.10.929"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.45.6.1721-1729.2001"},{"key":"e_1_3_2_12_2","first-page":"1","volume":"18","year":"1999","unstructured":"Dowell, S. F., J. C. Butler, G. S. Giebink, M. R. Jacobs, D. Jernigan, D. M. Musher, A. Rakowsky, and B. Schwartz. 1999. Acute otitis media: management and surveillance in an era of pneumococcal resistance\u2014a report from the Drug-Resistant Streptococcus pneumoniae Therapeutic Working Group. Pediatr. Infect. Dis. J.18:1-9.","journal-title":"Pediatr. Infect. Dis. J."},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.45.1.252-262.2001"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.2595372"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1843.2008.01422.x"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1080\/08923970701812746"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1910207"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.01913-06"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-009-0082-x"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.5.2689-2697.2004"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.68.2.492-501.2000"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2008-1702"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.032615"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.21201"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.294.16.2043"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(91)90124-H"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1086\/315009"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.2741\/McCullers"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0508961103"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1093\/clinids\/14.4.801"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200703-515OC"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1080\/00365540310015854"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199508243330802"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2008.06425.x"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.298.18.2155"},{"key":"e_1_3_2_36_2","doi-asserted-by":"crossref","first-page":"3869","DOI":"10.4049\/jimmunol.157.9.3869","volume":"157","year":"1996","unstructured":"Saha, B., B. Jaklic, D. M. Harlan, G. S. Gray, C. H. June, and R. Abe. 1996. Toxic shock syndrome toxin-1-induced death is prevented by CTLA4Ig. J. Immunol.157:3869-3875.","journal-title":"J. Immunol."},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.45.4.1037-1042.2001"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200210-1164OC"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.fjc.0000175233.88207.de"},{"key":"e_1_3_2_40_2","first-page":"970","volume":"337","year":"1997","unstructured":"Schuchat, A., K. Robinson, J. D. Wenger, L. H. Harrison, M. Farley, A. L. Reingold, L. Lefkowitz, and B. A. Perkins. 1997. Bacterial meningitis in the United States in 1995. Active Surveillance Team. N. Engl. J. Med.337:970-976.","journal-title":"Active Surveillance Team. N. Engl. J. Med."},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.3260404"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1086\/500941"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01403-06"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.10.7043-7046.2005"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/174.5.994"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.12.7603"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.11.7718-7726.2005"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200737295"},{"key":"e_1_3_2_49_2","doi-asserted-by":"crossref","first-page":"5885","DOI":"10.4049\/jimmunol.154.11.5885","volume":"154","year":"1995","unstructured":"Wallace, P. M., J. N. Rodgers, G. M. Leytze, J. S. Johnson, and P. S. Linsley. 1995. Induction and reversal of long-lived specific unresponsiveness to a T-dependent antigen following CTLA4Ig treatment. J. Immunol.154:5885-5895.","journal-title":"J. Immunol."},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa022823"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2004.08.007"}],"container-title":["Infection and Immunity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/IAI.00431-10","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/IAI.00431-10","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,3]],"date-time":"2023-06-03T12:01:34Z","timestamp":1685793694000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/IAI.00431-10"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,12]]},"references-count":50,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2010,12]]}},"alternative-id":["10.1128\/IAI.00431-10"],"URL":"https:\/\/doi.org\/10.1128\/iai.00431-10","relation":{},"ISSN":["0019-9567","1098-5522"],"issn-type":[{"value":"0019-9567","type":"print"},{"value":"1098-5522","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,12]]},"assertion":[{"value":"2010-04-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2010-09-10","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2010-12-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}