{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T14:58:51Z","timestamp":1767193131068},"reference-count":56,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2002,1,15]],"date-time":"2002-01-15T00:00:00Z","timestamp":1011052800000},"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":[[2002,1,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Viral persistence following infection with invasive strains of lymphocytic choriomeningitis virus (LCMV) can be achieved by selective down-regulation of virus-specific T lymphocytes. High viral burden in the onset of infection drives responding cells into functional unresponsiveness (anergy) that can be followed by their physical elimination. In this report, we studied down-regulation of the virus-specific CD8<jats:sup>+<\/jats:sup>-T-cell response during persistent infection of adult mice with LCMV, with emphasis on the role of perforin-, Fas\/FasL-, or tumor necrosis factor receptor 1 (TNFR1)-mediated cytolysis in regulating T-cell homeostasis. The results reveal that the absence of perforin, Fas-ligand, or TNFR1 has no significant effect on the kinetics of proliferation and functional inactivation of virus-specific CD8<jats:sup>+<\/jats:sup>T cells in the onset of chronic LCMV infection. However, these molecules play a critical role in the homeostatic regulation of T cells, influencing the longevity of the virus-specific CD8<jats:sup>+<\/jats:sup>-T-cell population once it has become anergic. Thus, CD8<jats:sup>+<\/jats:sup>T cells specific to the dominant LCMV NP<jats:sub>396\u2013404<\/jats:sub>epitope persist in an anergic state for at least 70 days in perforin-, FasL-, or TNFR1-deficient mice, but they were eliminated by day 30 in C57BL\/6 controls. These effects were additive as shown by a deficit of apoptotic death of NP<jats:sub>396\u2013404<\/jats:sub>peptide-specific CD8<jats:sup>+<\/jats:sup>T cells in mice lacking both perforin and TNFR1. This suggests a role for perforin-, FasL-, and TNFR1-mediated pathways in down-regulation of the antiviral T cell response during persistent viral infection by determining the fate of antigen-specific T cells. Moreover, virus-specific anergic CD8<jats:sup>+<\/jats:sup>T cells in persistently infected C57BL\/6 mice contain higher levels of Bcl-2 and Bcl-XL than functionally intact T cells generated during acute LCMV infection. In the case of proapoptotic factors, Bax expression did not differ between T-cell populations and Bad was below the limit of detection in all samples. As expression of the Bcl-2 family members controls susceptibility to apoptosis, this finding may provide a molecular basis for the survival of anergic cells under conditions of prolonged antigen stimulation.<\/jats:p>","DOI":"10.1128\/jvi.76.2.829-840.2002","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T09:55:53Z","timestamp":1027763753000},"page":"829-840","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":75,"title":["Critical Role for Perforin-, Fas\/FasL-, and TNFR1-Mediated Cytotoxic Pathways in Down-Regulation of Antigen-Specific T Cells during Persistent Viral Infection"],"prefix":"10.1128","volume":"76","author":[{"given":"Shenghua","family":"Zhou","sequence":"first","affiliation":[{"name":"Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, Georgia 30912"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rong","family":"Ou","sequence":"additional","affiliation":[{"name":"Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, Georgia 30912"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Huang","sequence":"additional","affiliation":[{"name":"Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, Georgia 30912"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Demetrius","family":"Moskophidis","sequence":"additional","affiliation":[{"name":"Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, Georgia 30912"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","first-page":"219","year":"1996","unstructured":"Ahmed, R., L. 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