title: Thymic plasmacytoid dendritic cells are susceptible to productive HIV-1 infection and efficiently transfer R5 HIV-1 to thymocytes in vitro.
abstract: BACKGROUND
  HIV-1 infection of the thymus contributes to the defective regeneration and loss of CD4+ T cells in HIV-1-infected individuals. As thymic dendritic cells (DC) are permissive to infection by HIV-1, we examined the ability of thymic DC to enhance infection of thymocytes which may contribute to the overall depletion of CD4+ T cells. We compared productive infection in isolated human thymic and blood CD11c+ myeloid DC (mDC) and CD123+ plasmacytoid DC (pDC) using enhanced green fluorescent protein (EGFP) CCR5 (R5)-tropic NL(AD8) and CXCR4 (X4)-tropic NL4-3 HIV-1 reporter viruses. Transfer of productive HIV-1 infection from thymic mDC and pDC was determined by culturing these DC subsets either alone or with sorted thymocytes.
  
  
  RESULTS
  Productive infection was observed in both thymic pDC and mDC following exposure to R5 HIV-1 and X4 HIV-1. Thymic pDC were more frequently productively infected by both R5 and X4 HIV-1 than thymic mDC (p = 0.03; n = 6). Thymic pDC efficiently transferred productive R5 HIV-1 infection to both CD3(hi) (p = 0.01; mean fold increase of 6.5; n = 6) and CD3(lo) thymocytes (mean fold increase of 1.6; n = 2). In comparison, transfer of productive infection by thymic mDC was not observed for either X4 or R5 HIV-1.
  
  
  CONCLUSIONS
  The capacity of thymic pDC to efficiently transfer R5 HIV-1 to both mature and immature thymocytes that are otherwise refractory to R5 virus may represent a pathway to early infection and impaired production of thymocytes and CD4+ T cells in HIV-1-infected individuals.
authors.affiliation: Monash University, Department of Medicine, Central and Eastern Clinical School, Alfred Campus, Commercial Rd., Melbourne, Victoria 3004, Australia.
authors.forename: Vanessa A
authors.initials: VA
authors.lastname: Evans
authors.forename: Luxshimi
authors.initials: L
authors.lastname: Lal
authors.forename: Ramesh
authors.initials: R
authors.lastname: Akkina
authors.forename: Ajantha
authors.initials: A
authors.lastname: Solomon
authors.forename: Edwina
authors.initials: E
authors.lastname: Wright
authors.forename: Sharon R
authors.initials: SR
authors.lastname: Lewin
authors.forename: Paul U
authors.initials: PU
authors.lastname: Cameron
mesh_terms: D039521:CD11c Antigen / Q000032:analysis; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D003713:Dendritic Cells / Q000737:chemistry / Q000821:virology*; D015497:HIV-1 / Q000254:growth & development*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D053650:Interleukin-3 Receptor alpha Subunit / Q000032:analysis; D016131:Lymphocyte Subsets / Q000821:virology; D019713:Receptors, CCR5 / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000378:metabolism; D015728:Receptors, HIV / Q000378:metabolism*; D013950:Thymus Gland / Q000821:virology*; D053586:Virus Internalization
chemical_list: D039521:CD11c Antigen; C527276:CXCR4 protein, human; C115022:IL3RA protein, human; D053650:Interleukin-3 Receptor alpha Subunit; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D015728:Receptors, HIV