{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T09:43:37Z","timestamp":1791020617582,"version":"4.1.0"},"reference-count":65,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2007,3,1]],"date-time":"2007-03-01T00:00:00Z","timestamp":1172707200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2007,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>HIV type 1 (HIV-1)-associated dementia (HAD) is believed to occur due to aberrant activation of monocyte-derived macrophages and brain-resident microglial cells by viral proteins as well as by the proinflammatory mediators released by infected cells. To investigate the inflammatory aspects of the disease, we examined the levels of soluble CD40L (sCD40L) in paired samples of plasma and cerebrospinal fluid obtained from 25 HIV-infected individuals. A significantly higher level of sCD40L was detected in both cerebrospinal fluid and plasma from HIV-infected patients with cognitive impairment, compared with their nonimpaired counterparts. The contribution of sCD40L to the pathogenesis of HAD was then examined by in vitro experiments. rCD40L synergized with HIV-1 Tat to increase TNF-\u03b1 release from primary human monocytes and microglia, in an NF-\u03baB-dependent manner. The mechanistic basis for this synergism was attributed to a Tat-mediated up-regulation of CD40 in monocytes and microglia. Finally, the CD40L-mediated increase in TNF-\u03b1 production by monocytes was shown to be biologically important; immunodepletion experiments revealed that TNF-\u03b1 was essential for the neurotoxic effects of conditioned medium recovered from Tat\/CD40L-treated monocytes. Taken together, our results show that CD40 signaling in microglia and monocytes can synergize with the effects of Tat, further amplifying inflammatory processes within the CNS and influencing neuronal survival.<\/jats:p>","DOI":"10.4049\/jimmunol.178.5.3226","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T13:14:39Z","timestamp":1397826879000},"page":"3226-3236","source":"Crossref","is-referenced-by-count":78,"title":["Functional Synergy between CD40 Ligand and HIV-1 Tat Contributes to Inflammation: Implications in HIV Type 1 Dementia"],"prefix":"10.1093","volume":"178","author":[{"given":"Ziye","family":"Sui","sequence":"first","affiliation":[{"name":"Interdepartmental Program in Neuroscience, University of Rochester School of Medicine and Dentistry , Rochester, NY 14642"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynn F","family":"Sniderhan","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry , Rochester, NY 14642"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Schifitto","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Rochester School of Medicine and Dentistry , Rochester, NY 14642"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard P","family":"Phipps","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry , Rochester, NY 14642"},{"name":"Department of Environmental Medicine, University of Rochester School of Medicine and Dentistry , Rochester, NY 14642"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harris A","family":"Gelbard","sequence":"additional","affiliation":[{"name":"Interdepartmental Program in Neuroscience, University of Rochester School of Medicine and Dentistry , Rochester, NY 14642"},{"name":"Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry , Rochester, NY 14642"},{"name":"Center for Aging and Development, University of Rochester School of Medicine and Dentistry , Rochester, NY 14642"},{"name":"Department of Neurology, University of Rochester School of Medicine and Dentistry , Rochester, NY 14642"},{"name":"Department of Pediatrics, University of Rochester School of Medicine and Dentistry , Rochester, NY 14642"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Dewhurst","sequence":"additional","affiliation":[{"name":"Interdepartmental Program in Neuroscience, University of Rochester School of Medicine and Dentistry , Rochester, NY 14642"},{"name":"Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry , Rochester, NY 14642"},{"name":"James P. 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