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CD8+ T cells plummet in number and quickly reach stable levels of memory following acute lymphocytic choriomeningitis virus infection in mice. In contrast, virus-specific CD4+ T cells gradually decrease in number and reach homeostatic levels only after many weeks. In this study, we provide evidence that MHCII-restricted viral Ag persists during the contraction phase following this prototypical acute virus infection. We evaluated whether the residual Ag affected the cell division and number of virus-specific naive and memory CD4+ T cells and CD8+ T cells. We found that naive CD4+ T cells underwent cell division and accumulated in response to residual viral Ag for &amp;gt;2 mo after the eradication of infectious virus. Surprisingly, memory CD4+ T cells did not undergo cell division in response to the lingering Ag, despite their heightened capacity to recognize Ag and make cytokine. In contrast to CD4+ T cells, CD8+ T cells did not undergo cell division in response to the residual Ag. Thus, CD8+ T cells ceased division within days after the infection was resolved, indicating that CD8+ T cell responses are tightly linked to endogenous processing of de novo synthesized virus protein. Our data suggest that residual viral Ag delays the contraction of CD4+ T cell responses by recruiting new populations of CD4+ T cells.<\/jats:p>","DOI":"10.4049\/jimmunol.1301215","type":"journal-article","created":{"date-parts":[[2013,10,21]],"date-time":"2013-10-21T22:13:25Z","timestamp":1382393605000},"page":"5655-5668","source":"Crossref","is-referenced-by-count":9,"title":["Differential T Cell Responses to Residual Viral Antigen Prolong CD4+ T Cell Contraction following the Resolution of Infection"],"prefix":"10.1093","volume":"191","author":[{"given":"Ichiro","family":"Misumi","sequence":"first","affiliation":[{"name":"Department of Genetics, University of North Carolina School of Medicine , Chapel Hill, NC 27599"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehrdad","family":"Alirezaei","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbial Sciences, Scripps Research Institute , La Jolla, CA 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boreth","family":"Eam","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbial Sciences, Scripps Research Institute , La Jolla, CA 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maureen A","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of North Carolina School of Medicine , Chapel Hill, NC 27599"},{"name":"Department of Pediatrics, University of North Carolina School of Medicine , Chapel Hill, NC 27599"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J Lindsay","family":"Whitton","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbial Sciences, Scripps Research Institute , La Jolla, CA 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason K","family":"Whitmire","sequence":"additional","affiliation":[{"name":"Department of Genetics, University of North Carolina School of Medicine , Chapel Hill, NC 27599"},{"name":"Department of Microbiology and Immunology, University of North Carolina School of Medicine , Chapel Hill, NC 27599"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,12,1]]},"reference":[{"key":"2025032406024798000_r1","doi-asserted-by":"crossref","first-page":"3028","DOI":"10.4049\/jimmunol.176.5.3028","article-title":"Precursor frequency, nonlinear proliferation, and functional maturation of virus-specific CD4+ T cells","volume":"176","author":"Whitmire","year":"2006","journal-title":"J. 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