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This pathology is induced by IAV-specific memory CD8<jats:sup>+<\/jats:sup>T cells cross-reactive with LCMV. Here, we discovered that IAV-immune mice have enhanced CD4<jats:sup>+<\/jats:sup>Foxp3<jats:sup>+<\/jats:sup>T-regulatory (Treg) cells in their lungs, leading us to question whether a modulation in the normal balance of Treg and effector T-cell responses also contributes to enhancing lung pathology upon LCMV infection of IAV-immune mice. Treg cell and interleukin-10 (IL-10) levels remained elevated in the lungs and mediastinal lymph nodes (mLNs) throughout the acute LCMV response of IAV-immune mice. PC61 treatment, used to decrease Treg cell levels, did not change LCMV titers but resulted in a surprising decrease in lung pathology upon LCMV infection in IAV-immune but not in naive mice. Associated with this decrease in pathology was a retention of Treg in the mLN and an unexpected partial clonal exhaustion of LCMV-specific CD8<jats:sup>+<\/jats:sup>T-cell responses only in IAV-immune mice. PC61 treatment did not affect cross-reactive memory CD8<jats:sup>+<\/jats:sup>T-cell proliferation. These results suggest that in the absence of IAV-expanded Treg cells and in the presence of cross-reactive memory, the LCMV-specific response was overstimulated and became partially exhausted, resulting in a decreased effector response. These studies suggest that Treg cells generated during past infections can influence the characteristics of effector T-cell responses and immunopathology during subsequent heterologous infections. Thus, in humans with complex infection histories, PC61 treatment may lead to unexpected results.<\/jats:p>","DOI":"10.1128\/jvi.00936-13","type":"journal-article","created":{"date-parts":[[2013,9,19]],"date-time":"2013-09-19T07:51:33Z","timestamp":1379577093000},"page":"12636-12647","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":15,"title":["PC61 (Anti-CD25) Treatment Inhibits Influenza A Virus-Expanded Regulatory T Cells and Severe Lung Pathology during a Subsequent Heterologous Lymphocytic Choriomeningitis Virus Infection"],"prefix":"10.1128","volume":"87","author":[{"given":"Anke R. 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