title: Mucosal immunization in macaques upregulates the innate APOBEC 3G anti-viral factor in CD4(+) memory T cells.
abstract: APOBEC3G is an innate intracellular anti-viral factor which deaminates retroviral cytidine to uridine. In vivo studies of APOBEC3G (A3G) were carried out in rhesus macaques, following mucosal immunization with SIV antigens and CCR5 peptides, linked to the 70kDa heat shock protein. A progressive increase in A3G mRNA was elicited in PBMC after each immunization (p<0.0002 to p< or =0.02), which was maintained for at least 17 weeks. Analysis of memory T cells showed a significant increase in A3G mRNA and protein in CD4(+)CCR5(+) memory T cells in circulating (p=0.0001), splenic (p=0.0001), iliac lymph nodes (p=0.002) and rectal (p=0.01) cells of the immunized compared with unimmunized macaques. Mucosal challenge with SIVmac 251 showed a significant increase in A3G mRNA in the CD4(+)CCR5(+) circulating cells (p<0.01) and the draining iliac lymph node cells (p<0.05) in the immunized uninfected macaques, consistent with a protective effect exerted by A3G. The results suggest that mucosal immunization in a non-human primate can induce features of a memory response to an innate anti-viral factor in CCR5(+)CD4(+) memory and CD4(+)CD95(+)CCR7(-) effector memory T cells.
authors.affiliation: Kings College London at Guy's Hospital, London SE1 9RT, England, UK.
authors.forename: Yufei
authors.initials: Y
authors.lastname: Wang
authors.forename: Lesley A
authors.initials: LA
authors.lastname: Bergmeier
authors.forename: Richard
authors.initials: R
authors.lastname: Stebbings
authors.forename: Thomas
authors.initials: T
authors.lastname: Seidl
authors.forename: Trevor
authors.initials: T
authors.lastname: Whittall
authors.forename: Mahavir
authors.initials: M
authors.lastname: Singh
authors.forename: Neil
authors.initials: N
authors.lastname: Berry
authors.forename: Neil
authors.initials: N
authors.lastname: Almond
authors.forename: Thomas
authors.initials: T
authors.lastname: Lehner
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D003564:Cytidine Deaminase / Q000096:biosynthesis*; D050884:HSP72 Heat-Shock Proteins / Q000008:administration & dosage / Q000494:pharmacology; D008198:Lymph Nodes / Q000276:immunology; D008253:Macaca mulatta; D009092:Mucous Membrane; D019713:Receptors, CCR5 / Q000008:administration & dosage; D012007:Rectum / Q000276:immunology; D018449:SAIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D013154:Spleen / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D050884:HSP72 Heat-Shock Proteins; D019713:Receptors, CCR5; D018449:SAIDS Vaccines; D003564:Cytidine Deaminase