title: Preferential feline immunodeficiency virus (FIV) infection of CD4+ CD25+ T-regulatory cells correlates both with surface expression of CXCR4 and activation of FIV long terminal repeat binding cellular transcriptional factors.
abstract: Previously, we have characterized feline CD4+ CD25+ T-regulatory (Treg) cells with regard to their immune regulatory properties and ability to support feline immunodeficiency virus (FIV) replication in vitro and in vivo. Our studies showed that while CD4+ CD25+ cells were capable of replicating FIV in the presence of interleukin-2 (IL-2) alone, CD4+ CD25- cells harbored a latent infection that required a strong mitogenic stimulus to activate virus replication. In the present study, we investigated the mechanisms governing the preferential replication of FIV in highly purified CD4+ CD25+ Treg cells compared to their CD4+ CD25+ counterparts. Studies aimed at elucidating mechanisms regulating infection of these cells revealed that CD4+ CD25- cells were less susceptible to FIV binding and entry than CD4+ CD25+ cells, which correlated with increased surface expression of FIV coreceptor CXCR4. In addition, the number of CD4+ CD25+ cells that expressed the primary receptor CD134 was greater than for CD4+ CD25- cells. Although increased permissiveness to FIV infection of CD4+ CD25- cells following mitogenic stimulation correlated strongly with upregulation of surface CXCR4, it did not correlate with CD134 expression. Further, study of intracellular factors regulating FIV replication revealed that CD4+ CD25+ but not CD4+ CD25- T cells showed constitutive and IL-2-responsive transactivation of activating transcription factor, CAAT enhancer binding protein, and activating protein 1 transcription factors that are important for FIV replication. These factors were upregulated in CD4+ CD25- T cells following ConA stimulation, which correlated with FIV replication. This is the first report elucidating the mechanisms that allow for productive lentiviral infection of CD4+ CD25+ Treg cells.
authors.affiliation: Immunology Program, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina 27606, USA.
authors.forename: Anjali
authors.initials: A
authors.lastname: Joshi
authors.forename: Himanshu
authors.initials: H
authors.lastname: Garg
authors.forename: Mary B
authors.initials: MB
authors.lastname: Tompkins
authors.forename: Wayne A
authors.initials: WA
authors.lastname: Tompkins
mesh_terms: D000818:Animals; D001596:Benzylamines; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D002415:Cats; D002478:Cells, Cultured; D000080027:Cyclams; D016181:Feline Acquired Immunodeficiency Syndrome / Q000276:immunology*; D006571:Heterocyclic Compounds / Q000494:pharmacology; D016089:Immunodeficiency Virus, Feline / Q000276:immunology / Q000502:physiology*; D008198:Lymph Nodes / Q000276:immunology / Q000821:virology; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors / Q000235:genetics*; D015375:Receptors, Interleukin-2 / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology; D014779:Virus Replication
chemical_list: D001596:Benzylamines; D000080027:Cyclams; D006571:Heterocyclic Compounds; D019718:Receptors, CXCR4; D015375:Receptors, Interleukin-2; C088327:plerixafor