{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T00:25:48Z","timestamp":1770078348353,"version":"3.49.0"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2001,3,1]],"date-time":"2001-03-01T00:00:00Z","timestamp":983404800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2001,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>IFN-\u03b3-deficient (IFN-\u03b3\u2212\/\u2212) mice inoculated with intermediate doses of a slowly replicating strain of lymphocytic choriomeningitis virus become chronically infected. In such mice a hypercompensated CTL response is observed that partially controls virus replication. Here we have investigated whether CD4+ Th cells are required to establish and maintain this new equilibrium. The absence of IFN-\u03b3 does not impair the generation of IL-2-producing CD4+ cells, and depletion of these cells precipitates severe CD8+ T cell-mediated immunopathology in IFN-\u03b3\u2212\/\u2212 mice, indicating an important role of CD4+ T cells in preventing this syndrome. Analysis of organ virus levels revealed a further impairment of virus control in IFN-\u03b3\u2212\/\u2212 mice following CD4+ cell depletion. Initially the antiviral CTL response did not require CD4+ cells, but with time an impaired reactivity toward especially the glycoprotein 33\u201341 epitope was noted. Enumeration of epitope-specific (glycoprotein 33\u201341 and nucleoprotein 396\u2013404) CD8+ T cells by use of tetramers gave similar results. Finally, limiting dilution analysis of CTL precursors reveal an impaired capacity to sustain this population in CD4+-depleted mice, especially in mice also deficient in IFN-\u03b3. Thus, our findings disclose that T cell help is required to sustain the expanded CTL precursor pool required in IFN-\u03b3\u2212\/\u2212 mice. This interpretation is supported by mathematical modeling that predicts an increased requirement for help in IFN-\u03b3\u2212\/\u2212 hosts similar to what is found with fast replicating virus strains in normal hosts. Thus, the functional integrity of CD8+ effector T cells is one important factor influencing the requirement for T cell help during viral infection.<\/jats:p>","DOI":"10.4049\/jimmunol.166.5.3384","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T23:20:12Z","timestamp":1398036012000},"page":"3384-3391","source":"Crossref","is-referenced-by-count":21,"title":["Depletion of CD4+ T Cells Precipitates Immunopathology in Immunodeficient Mice Infected with a Noncytocidal Virus"],"prefix":"10.1093","volume":"166","author":[{"given":"Jan Pravsgaard","family":"Christensen","sequence":"first","affiliation":[{"name":"Institute of Medical Microbiology and Immunology, University of Copenhagen , Copenhagen ,","place":["Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christina","family":"Bartholdy","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology and Immunology, University of Copenhagen , Copenhagen ,","place":["Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dominik","family":"Wodarz","sequence":"additional","affiliation":[{"name":"Institute for Advanced Study , Princeton, NJ 08540"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Allan Randrup","family":"Thomsen","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology and Immunology, University of Copenhagen , Copenhagen ,","place":["Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2001,3,1]]},"reference":[{"key":"2026020208033799000_R1","first-page":"381","volume-title":"J. 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