Soluble CD40 ligand contributes to dendritic cell-mediated T-cell dysfunction in HIV-1 infection. (17th July 2015)

• Record Type: Journal Article
• Authors: Miller, Elizabeth A.; Gopal, Ramya; Valdes, Vanessa; Berger, Jeffrey S.; Bhardwaj, Nina; O'Brien, Meagan P.
• Is Part Of: AIDS. Volume 29:Number 11(2015)
• Publication Date: 2015-07-17
• Subjects: HIV-1 -- innate immunity -- interleukin-12 -- myeloid dendritic cell -- soluble CD40 ligand -- Toll-like receptor; AIDS (Disease) -- Periodicals; Acquired Immunodeficiency Syndrome; AIDS (Disease); Periodicals; Periodicals; 616.9792005
• DOI: 10.1097/QAD.0000000000000698
• Languages: English
• ISSNs: 0269-9370

Abstract

Abstract : Objective: Plasma soluble CD40 ligand (sCD40L) is increased during HIV-1 infection, but it is unknown whether it circulates in monomeric or multimeric forms, and whether the circulating forms have differential effects on myeloid dendritic cell function and adaptive regulation. Design: sCD40L forms were measured in plasma samples from HIV-infected donors. The effects of sCD40L forms on dendritic cell function were measured in vitro . Methods: To delineate which forms of sCD40L are present in plasma from HIV-infected donors, immunoblots were performed following enrichment of plasma for medium and low-abundance proteins. Dendritic cells from seronegative donors were exposed to multiple forms of sCD40L prior to Toll-like receptor stimulation and dendritic cell function and adaptive regulation was assessed in vitro . Results: Monomeric and multimeric forms of sCD40L were identified in plasma from antiretroviral therapy-treated HIV-infected donors. Although monomeric and multimeric forms of sCD40L had differential effects on dendritic cell activation when given alone, both strongly suppressed secretion of the Th1 skewing cytokine, interleukin-12, upon subsequent Toll-like receptor stimulation. Furthermore, dendritic cells exposed to both monomeric and multimeric sCD40L induced regulatory T-cell formation and T-cell anergy. Conclusion: Elevated sCD40L during HIV infection impairs dendritic cell function, contributing to innate and adaptive immune dysfunction. Antiretroviral adjunctive therapies that decrease sCD40L may provide immune modulatory benefits. Abstract : Supplemental Digital Content is available in the text