title: Naive CD4 T cells inhibit CD28-costimulated R5 HIV replication in memory CD4 T cells.
abstract: Stimulation with antibodies to CD3 and CD28 coimmobilized on beads can be used to significantly expand T cells ex vivo. With CD4 T cells from HIV-infected patients, this expansion usually is accompanied by complete suppression of viral replication, presumed to be caused by down-regulation of the viral coreceptor CCR5 and up-regulation of CCR5 ligands. Here we show that this suppression occurs in total CD4 T cells acutely infected with R5 HIV, but not in purified CD62L(-) memory CD4 T cells. The lack of complete suppression in these memory cells, typically comprising 10-40% of total CD4 T cells, occurs despite high levels of CCR5 ligand secretion and down-regulation of CCR5. Significantly, adding back naive or CD62L(+) memory CD4 T cells inhibits the viral replication in the CD62L(-) cells, with the naive cells capable of completely repressing the virus. Although this inhibition was previously thought to be specific to bead-bound anti-CD3/CD28 stimulation, we show that the same suppression is obtained with sufficiently strong anti-CD3/B7.1 stimulation. Our results show that inhibitory mechanisms, expressed predominantly by strongly stimulated naive CD4 T cells and mediated independently of CCR5-binding chemokines, play a role in the inhibition of R5 HIV replication in CD4 T cells upon CD28 costimulation.
authors.affiliation: Department of Genetics, Stanford University, Stanford, CA 94305-5318, USA.
authors.forename: M
authors.initials: M
authors.lastname: Mengozzi
authors.forename: M
authors.initials: M
authors.lastname: Malipatlolla
authors.forename: S C
authors.initials: SC
authors.lastname: De Rosa
authors.forename: L A
authors.initials: LA
authors.lastname: Herzenberg
authors.forename: L A
authors.initials: LA
authors.lastname: Herzenberg
authors.forename: M
authors.initials: M
authors.lastname: Roederer
mesh_terms: D015703:Antigens, CD / Q000032:analysis; D018106:CD28 Antigens / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D005434:Flow Cytometry / Q000379:methods; D006678:HIV / Q000276:immunology / Q000502:physiology*; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory / Q000502:physiology*; D008213:Lymphocyte Activation; D016853:Muromonab-CD3 / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014779:Virus Replication
chemical_list: D015703:Antigens, CD; D018106:CD28 Antigens; D017252:CD3 Complex; D016853:Muromonab-CD3