{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T04:56:31Z","timestamp":1789188991807,"version":"build-2803163510"},"reference-count":29,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2003,1,1]],"date-time":"2003-01-01T00:00:00Z","timestamp":1041379200000},"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":[[2003,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Cell-mediated immune (CMI) responses and tumor necrosis factor alpha (TNF-\u03b1) have been shown to be essential in acquired protection against<jats:italic>Cryptococcus neoformans<\/jats:italic>. Induction of a protective anticryptococcal CMI response includes increases in dendritic cells (DC) and activated CD4<jats:sup>+<\/jats:sup>T cells in draining lymph nodes (DLN). During the expression phase, activated CD4<jats:sup>+<\/jats:sup>T cells accumulate at a peripheral site where cryptococcal antigen is injected, resulting in a classical delayed-type hypersensitivity (DTH) reaction. Induction of a nonprotective anticryptococcal CMI response results in no significant increases in the numbers of DC or activated CD4<jats:sup>+<\/jats:sup>T cells in DLN. This study focuses on examining the role of TNF-\u03b1 in induction of protective and nonprotective anticryptococcal CMI responses. We found that neutralization of TNF-\u03b1 at the time of immunization with the protective immunogen (i) reduces the numbers of Langerhans cells, myeloid and lymphoid DC, and activated CD4<jats:sup>+<\/jats:sup>T cells in DLN and (ii) diminishes the total numbers of cells, the numbers of activated CD4<jats:sup>+<\/jats:sup>T cells, and amount of gamma interferon at the DTH reaction site. Although TNF-\u03b1 neutralization during induction of the nonprotective CMI response had little effect on cellular and cytokine parameters measured, it did cause a reduction in footpad swelling when mice received challenge in the footpad. Our findings show that TNF-\u03b1 functions during induction of the protective CMI response by influencing the accumulation of all three DC subsets into DLN. Without antigen stimulated DC in DLN, activated CD4<jats:sup>+<\/jats:sup>T cells are not induced and thus not available for the expression phase of the CMI response.<\/jats:p>","DOI":"10.1128\/iai.71.1.68-74.2003","type":"journal-article","created":{"date-parts":[[2002,12,20]],"date-time":"2002-12-20T23:07:23Z","timestamp":1040425643000},"page":"68-74","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":61,"title":["Effects of Tumor Necrosis Factor Alpha on Dendritic Cell Accumulation in Lymph Nodes Draining the Immunization Site and the Impact on the Anticryptococcal Cell-Mediated Immune Response"],"prefix":"10.1128","volume":"71","author":[{"given":"Sean K.","family":"Bauman","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73190"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary B.","family":"Huffnagle","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, Michigan 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juneann W.","family":"Murphy","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73190"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.1.158"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.61.7.2854-2865.1993"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2567.1997.00144.x"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.62.7.2930-2939.1994"},{"key":"e_1_3_2_6_2","doi-asserted-by":"crossref","unstructured":"Casadevall A. and J. 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