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Memory T cells survive and undergo homeostatic proliferation (HSP) in the absence of Ag, although the cell-intrinsic mechanisms by which cytokines drive the HSP of memory T cells are not well understood. In this study we report that lysosome stability limits the long-term maintenance of memory CD8+ T cell populations. Serine protease inhibitor (Spi) 2A, an anti-apoptotic cytosolic cathepsin inhibitor, is induced by both IL-15 and IL-7. Mice deficient in Spi2A developed fewer memory phenotype CD44hiCD8+ T cells with age, which underwent reduced HSP in the bone marrow. Spi2A was also required for the maintenance of central memory CD8+ T cell populations after acute infection with lymphocytic choriomeningitis virus. Spi2A-deficient Ag-specific CD8+ T cell populations declined more than wild-type competitors after viral infection, and they were eroded further after successive infections. Spi2A protected memory cells from lysosomal breakdown by inhibiting cathepsin B. The impaired maintenance of Spi2A-deficient memory CD8+ T cells was rescued by concomitant cathepsin B deficiency, demonstrating that cathepsin B was a physiological target of Spi2A in memory CD8+ T cell survival. Our findings support a model in which protection from lysosomal rupture through cytokine-induced expression of Spi2A determines the long-term persistence of memory CD8+ T cells.<\/jats:p>","DOI":"10.4049\/jimmunol.1003406","type":"journal-article","created":{"date-parts":[[2012,6,28]],"date-time":"2012-06-28T00:56:25Z","timestamp":1340844985000},"page":"1133-1143","source":"Crossref","is-referenced-by-count":27,"title":["Cathepsin B Controls the Persistence of Memory CD8+ T Lymphocytes"],"prefix":"10.1093","volume":"189","author":[{"given":"Susan M","family":"Byrne","sequence":"first","affiliation":[{"name":"Section of Immunobiology, Division of Immunology and Inflammation, Department of Medicine, Faculty of Medicine, Imperial College London , London W12 0NN,","place":["United Kingdom"]},{"name":"Committee on Immunology, University of Chicago , Chicago, IL 60637"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Aucher","sequence":"additional","affiliation":[{"name":"Section of Immunology and Infection, Division of Cell and Molecular Biology, Imperial College London , London SW7 2AZ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syarifah","family":"Alyahya","sequence":"additional","affiliation":[{"name":"Section of Immunobiology, Division of Immunology and Inflammation, Department of Medicine, Faculty of Medicine, Imperial College London , London W12 0NN,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Elder","sequence":"additional","affiliation":[{"name":"Section of Immunobiology, Division of Immunology and Inflammation, Department of Medicine, Faculty of Medicine, Imperial College London , London W12 0NN,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven T","family":"Olson","sequence":"additional","affiliation":[{"name":"Center for Molecular Biology of Oral Diseases, University of Illinois at Chicago , Chicago, IL 60612"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel M","family":"Davis","sequence":"additional","affiliation":[{"name":"Section of Immunology and Infection, Division of Cell and Molecular Biology, Imperial College London , London SW7 2AZ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip G","family":"Ashton-Rickardt","sequence":"additional","affiliation":[{"name":"Section of Immunobiology, Division of Immunology and Inflammation, Department of Medicine, Faculty of Medicine, Imperial College London , London W12 0NN,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2012,8,1]]},"reference":[{"key":"2025032409215377200_r1","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1146\/annurev.immunol.20.100101.151926","article-title":"T cell memory","volume":"20","author":"Sprent","year":"2002","journal-title":"Annu. 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Med."},{"key":"2025032409215377200_r40","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/S0047-6374(97)01893-9","article-title":"Age-related changes in T cell surface markers: a longitudinal analysis in genetically heterogeneous mice","volume":"96","author":"Miller","year":"1997","journal-title":"Mech. Ageing Dev."},{"key":"2025032409215377200_r41","doi-asserted-by":"crossref","first-page":"7654","DOI":"10.4049\/jimmunol.174.12.7654","article-title":"CD8 cell division maintaining cytotoxic memory occurs predominantly in the bone marrow","volume":"174","author":"Parretta","year":"2005","journal-title":"J. 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Liver Physiol."},{"key":"2025032409215377200_r47","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1084\/jem.20021952","article-title":"Lysosomal membrane permeabilization induces cell death in a mitochondrion-dependent fashion","volume":"197","author":"Boya","year":"2003","journal-title":"J. Exp. Med."},{"key":"2025032409215377200_r48","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1016\/j.it.2007.08.008","article-title":"Regulated secretion from CD4+ T cells","volume":"28","author":"Jolly","year":"2007","journal-title":"Trends Immunol."},{"key":"2025032409215377200_r49","doi-asserted-by":"crossref","first-page":"4751","DOI":"10.1021\/cr010170+","article-title":"Serpin structure, mechanism, and function","volume":"102","author":"Gettins","year":"2002","journal-title":"Chem. 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