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However, a full understanding of the requirements for alternative activation, particularly at the innate level, is lacking. We present evidence that alternative activation by the Th2 cytokines IL-4 and IL-13 is an innate and rapid response to tissue injury that takes place even in the absence of an infectious agent. This early response does not require CD4+ Th2 cells because it occurred in RAG-deficient mice. However, class II-restricted CD4+ T cell help is essential to maintain AAM\u03a6 in response to infection, because AAM\u03a6 were absent in RAG-deficient and MHC class II-deficient, but not B cell-deficient mice after chronic exposure to the nematode parasite, Brugia malayi. The absence of AAM\u03a6 was associated with increased neutrophilia and reduced eosinophilia, suggesting that AAM\u03a6 are involved in the clearance of neutrophils as well as the recruitment of eosinophils. Consistent with this hypothesis, AAM\u03a6 show enhanced phagocytosis of apoptotic neutrophils, but not latex beads. Our data demonstrate that alternative activation by type 2 cytokines is an innate response to injury that can occur in the absence of an adaptive response. However, analogous to classical activation by microbial pathogens, Th2 cells are required for maintenance and full activation during the ongoing response to metazoan parasites.<\/jats:p>","DOI":"10.4049\/jimmunol.179.6.3926","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T19:32:36Z","timestamp":1397849556000},"page":"3926-3936","source":"Crossref","is-referenced-by-count":229,"title":["Alternative Activation Is an Innate Response to Injury That Requires CD4+ T Cells to be Sustained during Chronic Infection"],"prefix":"10.1093","volume":"179","author":[{"given":"P\u2019ng","family":"Loke","sequence":"first","affiliation":[{"name":"Tropical Disease Research Unit, University of California , San Francisco, CA 94143"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iain","family":"Gallagher","sequence":"additional","affiliation":[{"name":"Institutes of Evolution, Immunology, and Infection Research, University of Edinburgh , Edinburgh ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meera G","family":"Nair","sequence":"additional","affiliation":[{"name":"Institutes of Evolution, Immunology, and Infection Research, University of Edinburgh , Edinburgh ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingxing","family":"Zang","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, Memorial Sloan-Kettering Cancer Center , New York, NY 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Brombacher","sequence":"additional","affiliation":[{"name":"Institute of Infectious Disease and Molecular Medicine, University of Capetown ,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Mohrs","sequence":"additional","affiliation":[{"name":"Trudeau Institute , Saranac Lake, NY 12983"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James P","family":"Allison","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, Memorial Sloan-Kettering Cancer Center , New York, NY 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith E","family":"Allen","sequence":"additional","affiliation":[{"name":"Institutes of Evolution, Immunology, and Infection Research, University of Edinburgh , Edinburgh ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2007,9,15]]},"reference":[{"key":"2026012809323935200_R1","first-page":"23","volume-title":"Nat. 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