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We showed previously that chronic exposure to blood-stage<jats:named-content content-type=\"genus-species\">Plasmodium chabaudi<\/jats:named-content>offers the best protection from parasitemia and pathology in reinfection cases, correlating with an increase in Th1 cells. Although much is known about the features of resting or exhausted memory T cells (Tmem), little is known about the functional capacities of chronically stimulated but protective T cells. To determine the functional capacity of CD4 T cells generated by chronic infection upon reexposure to parasite, we compared their responses to known features of classical Tmem. The numbers of cytokine-producing T cells increased following infection in the polyclonal populations, suggesting an increase in pathogen-specific T cells. Malaria antigen-specific B5 T cell receptor (TCR) transgenic (Tg) T cells from chronic infection proliferated on reinfection and were highly sensitive to TCR stimulation without costimulation, as shown for Tmem in acute stimulations. However, B5 Tmem did not accumulate more than naive B5 T cells<jats:italic>in vivo<\/jats:italic>or<jats:italic>in vitro<\/jats:italic>and became apoptotic. Failure to accumulate was partly the result of chronic stimulation, since eliminating persistent parasites before reinfection slightly increased the accumulation of B5 Tg T cells upon reinfection. The levels of specific gamma interferon-positive, interleukin-10-positive T cells, which protect animals from pathology, increased after malaria infection. These data demonstrate that although chronic infection generates a protective T cell population with increased TCR sensitivity and cytokine production, they do not reexpand upon reexposure due to increased apoptosis.<\/jats:p>","DOI":"10.1128\/iai.00744-16","type":"journal-article","created":{"date-parts":[[2016,12,29]],"date-time":"2016-12-29T02:40:48Z","timestamp":1482979248000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":10,"title":["Chronic Plasmodium chabaudi Infection Generates CD4 Memory T Cells with Increased T Cell Receptor Sensitivity but Poor Secondary Expansion and Increased Apoptosis"],"prefix":"10.1128","volume":"85","author":[{"given":"Michael M.","family":"Opata","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Division of Infectious Diseases, University of Texas Medical Branch, Galveston, Texas, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robin","family":"Stephens","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Infectious Diseases, University of Texas Medical Branch, Galveston, Texas, USA"},{"name":"Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0024852"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1001208"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1080\/00034989859366"},{"key":"e_1_3_2_5_2","first-page":"71","article-title":"Longevity of the immune response and memory to blood-stage malaria infection","volume":"297","author":"Achtman AH","year":"2005","unstructured":"Achtman AH Bull PC Stephens R Langhorne J . 2005. 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