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Although much has been learned about the role of CMI in the clearance of<jats:italic>C. neoformans<\/jats:italic>from the lungs and other internal organs, less is known about the protective mechanisms in the brain, the organ most frequently involved with a fatal outcome of cryptococcosis. We hypothesized that host resistance mechanisms against<jats:italic>C. neoformans<\/jats:italic>in the central nervous system (CNS) were similar to those outside the CNS (i.e., gamma interferon [IFN-\u03b3], CD4<jats:sup>+<\/jats:sup>T cells, and others). To test this hypothesis, we used a murine model of cryptococcal meningitis whereby cryptococci are introduced directly into the CNS. In experiments where mice were immunized to mount an anticryptococcal CMI response, our results indicate that immunization induced protective mechanisms that could be detected in the CNS by inhibition of the growth of viable yeast cells. Flow cytometric analyses of leukocytes in brain and spinal cord homogenates revealed that T lymphocytes, macrophages, and neutrophils accumulated in<jats:italic>C. neoformans<\/jats:italic>-infected brains of immune mice. In vivo depletion of CD4<jats:sup>+<\/jats:sup>T cells, but not CD8<jats:sup>+<\/jats:sup>T cells, resulted in significantly reduced leukocyte accumulation in the brains of immune mice. Furthermore, depletion of CD4<jats:sup>+<\/jats:sup>T cells or neutralization of IFN-\u03b3 exacerbated CNS infection in immune mice, suggesting a critical role for CMI mechanisms in acquired protection in the CNS.<\/jats:p>","DOI":"10.1128\/iai.68.2.456-462.2000","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T10:01:19Z","timestamp":1027764079000},"page":"456-462","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":65,"title":["Requirement for CD4<sup>+<\/sup>T Lymphocytes in Host Resistance against<i>Cryptococcus neoformans<\/i>in the Central Nervous System of Immunized Mice"],"prefix":"10.1128","volume":"68","author":[{"given":"Kent L.","family":"Buchanan","sequence":"first","affiliation":[{"name":"<!--label omitted: 1-->Department of Microbiology and Immunology, Tulane University Medical Center, New Orleans, Louisiana 70112,1 and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hester A.","family":"Doyle","sequence":"additional","affiliation":[{"name":"<!--label omitted: 2-->Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 731902"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.63.5.1725-1731.1995"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.63.4.1218-1222.1995"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0165-5728(95)00016-U"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.61.7.2854-2865.1993"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2567.1997.00144.x"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.23.3.644-651.1979"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4612-3730-3_2"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-2776(08)60209-6"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1021\/ac60111a017"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/0167-5699(94)90247-X"},{"key":"e_1_3_2_12_2","doi-asserted-by":"crossref","first-page":"3219","DOI":"10.4049\/jimmunol.142.9.3219","article-title":"Fungicidal activity of IFN-gamma-activated macrophages. 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