title: Replication of the human immunodeficiency virus 1 and impaired differentiation of T cells after in vitro infection of bone marrow immature T cells.
abstract: HIV-1 infection in vitro of normal bone marrow mononuclear cells (BMMC) depleted of mature T cells was studied. BMMC depleted of either CD3, CD2, or both could replicate HIV-1 irrespective of the presence of macrophages/monocytes. Infected bone marrow cells were shown to differentiate during the culture into CD3+, CD4+, CD8+, and CD1+ cells, whereas noninfected BMMC gave rise to CD3+, CD4+, and CD8+ cells. Moreover, 9-14% of the cells also expressed the viral proteins p24 and gp120 on their surface. Double staining studies revealed that 72 and 83% of the CD4+ cells expressed the gp120 and p24, respectively, suggesting that virus replication occurred in CD4+ cells. T cell colony growth from infected BMMC, either unfractionated or depleted of mature T cells, was impaired in a time-dependent manner, and the differentiation capacity of T cell precursors was abnormal. Colony cells displayed an immature cell phenotype (CD1+ cells) and the viral proteins gp120 and/or p24 could also be detected on CD1+ cells. In addition, pooled colony cells derived from infected CD2- and CD3-depleted BMMC could infect normal mitogen-activated lymphocytes in coculture experiments. These findings strongly suggest that HIV-1 can infect immature bone marrow T cells and be transmitted to the progeny, but the massive viral replication occurs only when the cells differentiate toward CD4+ cells.
authors.affiliation: Unité d'Oncogénèse Appliquée (Institut Nationale de la Santé et de la Recherche Medicale), Hôpital Paul Brousse, Villejuif, France.
authors.forename: Y
authors.initials: Y
authors.lastname: Lunardi-Iskandar
authors.forename: M T
authors.initials: MT
authors.lastname: Nugeyre
authors.forename: V
authors.initials: V
authors.lastname: Georgoulias
authors.forename: F
authors.initials: F
authors.lastname: Barré-Sinoussi
authors.forename: C
authors.initials: C
authors.lastname: Jasmin
authors.forename: J C
authors.initials: JC
authors.lastname: Chermann
mesh_terms: D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D001853:Bone Marrow / Q000382:microbiology*; D001854:Bone Marrow Cells; D018801:CD2 Antigens; D017252:CD3 Complex; D016827:CD8 Antigens; D002454:Cell Differentiation; D002455:Cell Division; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D010641:Phenotype; D011948:Receptors, Antigen, T-Cell / Q000032:analysis; D011971:Receptors, Immunologic / Q000032:analysis; D013601:T-Lymphocytes / Q000166:cytology / Q000382:microbiology*; D014779:Virus Replication
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D017252:CD3 Complex; D016827:CD8 Antigens; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic