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CD4<jats:sup>+<\/jats:sup>T lymphocytes are critical for host defense against this infection, but in the absence of CD4<jats:sup>+<\/jats:sup>T lymphocytes, CD8<jats:sup>+<\/jats:sup>T lymphocytes may provide limited host defense. The cytokine interleukin-7 (IL-7) functions to enhance lymphocyte proliferation, survival, and recruitment of immune cells to sites of infection. However, there is little known about the role of IL-7 in PCP or its potential use as an immunotherapeutic agent. We hypothesized that treatment with recombinant human IL-7 (rhIL-7) would augment host defense against<jats:named-content content-type=\"genus-species\">Pneumocystis<\/jats:named-content>and accelerate pathogen clearance in CD4-depleted mice. Control and CD4-depleted mice were infected with<jats:named-content content-type=\"genus-species\">Pneumocystis<\/jats:named-content>, and rhIL-7 was administered via intraperitoneal injection. Our studies indicate that endogenous murine IL-7 is part of the normal host response to<jats:named-content content-type=\"genus-species\">Pneumocystis murina<\/jats:named-content>and that administration of rhIL-7 markedly enhanced clearance of<jats:named-content content-type=\"genus-species\">Pneumocystis<\/jats:named-content>in CD4-depleted mice. Additionally, we observed increased recruitment of CD8<jats:sup>+<\/jats:sup>T lymphocytes to the lungs and decreased apoptosis of pulmonary CD8<jats:sup>+<\/jats:sup>T lymphocytes in rhIL-7-treated animals compared to those in untreated mice. The antiapoptotic effect of rhIL-7 was associated with increased levels of Bcl-2 protein in T lymphocytes. rhIL-7 immunotherapy in CD4-depleted mice also increased the number of gamma interferon (IFN-\u03b3)-positive CD8<jats:sup>+<\/jats:sup>central memory T lymphocytes in the lungs. We conclude that rhIL-7 has a potent therapeutic effect in the treatment of murine<jats:named-content content-type=\"genus-species\">Pneumocystis<\/jats:named-content>pneumonia in CD4-depleted mice. This therapeutic effect is mediated through enhanced recruitment of CD8<jats:sup>+<\/jats:sup>T cells and decreased apoptosis of lung T lymphocytes, with a preferential action on central memory CD8<jats:sup>+<\/jats:sup>T lymphocytes.<\/jats:p>","DOI":"10.1128\/iai.01189-15","type":"journal-article","created":{"date-parts":[[2015,10,20]],"date-time":"2015-10-20T12:29:14Z","timestamp":1445344154000},"page":"108-119","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":18,"title":["Treatment with Interleukin-7 Restores Host Defense against Pneumocystis in CD4<sup>+<\/sup>T-Lymphocyte-Depleted Mice"],"prefix":"10.1128","volume":"84","author":[{"given":"S.","family":"Ruan","sequence":"first","affiliation":[{"name":"Section of Pulmonary\/Critical Care &amp; Allergy\/Immunology, Department of Medicine, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. 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