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We used timed deletion of the TCR-signaling adaptor molecule Src homology 2 domain-containing phosphoprotein of 76 kDa (SLP-76) with MHC:peptide tetramers to study the requirements for tonic TCR signals in the maintenance of polyclonal Ag-specific CD4+ memory T cells. SLP-76\u2013deficient I-Ab:gp61 cells are unable to rapidly generate effector cytokines or proliferate in response to secondary infection. In mice infected with lymphocytic choriomeningitis virus (LCMV) or Listeria monocytogenes expressing the LCMV gp61\u201380 peptide, SLP-76\u2013deficient I-Ab:gp61+ cells exhibit reduced division, similar to that seen in in vitro-generated CD44hi and endogenous CD4+CD44hi cells. Competitive bone marrow chimera experiments demonstrated that the decrease in homeostatic turnover in the absence of SLP-76 is a cell-intrinsic process. Surprisingly, despite the reduction in turnover, I-Ab:gp61+ Ag-specific memory cells persist in normal numbers for &amp;gt;30 wk after LCMV infection in the absence of SLP-76. These data suggest the independent maintenance of a population of Ag-specific CD4+ memory T cells in the absence of SLP-76 and normal levels of homeostatic division.<\/jats:p>","DOI":"10.4049\/jimmunol.1201583","type":"journal-article","created":{"date-parts":[[2012,9,7]],"date-time":"2012-09-07T00:26:14Z","timestamp":1346977574000},"page":"3378-3385","source":"Crossref","is-referenced-by-count":3,"title":["Homeostatic Division Is Not Necessary for Antigen-Specific CD4+ Memory T Cell Persistence"],"prefix":"10.1093","volume":"189","author":[{"given":"Evann","family":"Corbo-Rodgers","sequence":"first","affiliation":[{"name":"Immunology Graduate Group, University of Pennsylvania , Philadelphia, PA 19104"},{"name":"Renal-Electrolyte and Hypertension Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania School of Medicine , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karla R","family":"Wiehagen","sequence":"additional","affiliation":[{"name":"Immunology Graduate Group, University of Pennsylvania , Philadelphia, PA 19104"},{"name":"Renal-Electrolyte and Hypertension Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania School of Medicine , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth S","family":"Staub","sequence":"additional","affiliation":[{"name":"Renal-Electrolyte and Hypertension Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania School of Medicine , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan S","family":"Maltzman","sequence":"additional","affiliation":[{"name":"Immunology Graduate Group, University of Pennsylvania , Philadelphia, PA 19104"},{"name":"Renal-Electrolyte and Hypertension Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania School of Medicine , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2012,10,1]]},"reference":[{"key":"2025032409280296300_r1","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1111\/j.0105-2896.2006.00401.x","article-title":"Homeostasis of memory T cells","volume":"211","author":"Surh","year":"2006","journal-title":"Immunol. 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