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We addressed this important question in a mouse model of ocular HSV-1 infection, where sensory nerve damage is a common clinical problem. Through genetic and pharmacologic targeting, we uncovered a central role for C3 in sensory nerve damage at the morphological and functional levels. Interestingly, CD4 T cells were central in facilitating this complement-mediated damage. This same C3\/CD4 T cell axis triggered corneal sensory nerve damage in a mouse model of ocular graft-versus-host disease (GVHD). However, this was not the case in a T-dependent allergic eye disease (AED) model, suggesting that this inflammatory neuroimmune pathology is specific to certain disease etiologies. Collectively, these findings uncover a central role for complement in CD4 T cell-dependent corneal nerve damage in multiple disease settings and indicate the possibility for complement-targeted therapeutics to mitigate sensory neuropathies.<\/jats:p>","DOI":"10.7554\/elife.48378","type":"journal-article","created":{"date-parts":[[2019,8,15]],"date-time":"2019-08-15T08:00:24Z","timestamp":1565856024000},"source":"Crossref","is-referenced-by-count":42,"title":["Complement and CD4+ T cells drive context-specific corneal sensory neuropathy"],"prefix":"10.7554","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8476-1784","authenticated-orcid":true,"given":"Derek J","family":"Royer","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Duke University Medical Center, Durham, United States"},{"name":"Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, United 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