Limited expression of R5-tropic HIV-1 in CCR5-positive type 1-polarized T cells explained by their ability to produce RANTES, MIP-1alpha, and MIP-1beta.
Human T helper (Th) cells (Th1- or Th2-oriented memory T cells as well as Th1- or Th2-polarized naive T cells) were infected in vitro with an R5-tropic HIV-1 strain (BaL) and assessed for their profile of cytokine production, CCR5 receptor expression, and HIV-1 p24 antigen (p24 Ag) production. Higher p24 Ag production was found in CCR5-negative Th2-like memory T cells than in CCR5-positive Th1-like memory T cells. By contrast, p24 Ag production was higher in Th1-polarized activated naive T cells in the first 4 days after infection. However, p24 Ag production in Th1-polarized T cells became comparable or even lower than the production in Th2-polarized populations later in infection or when the cells were infected with HIV-1BaL after secondary stimulation. The higher levels of p24 Ag production by Th1-polarized naive T cells soon after infection reflected a higher virus entry, as assessed by the single round infection assay using the HIV-chloramphenicol acetyl transferase (HIV-CAT) R5-tropic virus that contains the envelope protein of HIV-1 YU2 strain. The limitation of viral spread in the Th1-polarized populations, despite the initial higher level of T-cell entry of R5-tropic strains, was due to the ability of Th1 cells to produce greater amounts of beta-chemokines than Th2 cells. In fact, an inverse correlation was observed between Th1-polarized naive T cells and Th1-like memory-activated T cells in regards to p24 Ag production and the release of the following CCR5-binding chemokines: regulated on activation normal T expressed and secreted (RANTES), macrophage inflammatory protein-1alpha (MIP-1alpha), and MIP-1beta. Moreover, infection with the HIV-1BaL strain of Th1-polarized T cells in the presence of a mixture of anti-RANTES, anti-MIP-1alpha, and anti-MIP-1beta neutralizing antibodies resulted in a significant increase of HIV-1 expression. These findings suggest that Th1-type responses may favor CD4(+) T-cell infection by R5-tropic HIV-1 strains, but HIV-1 spread in Th1 cells is limited by their ability to produce CCR5-binding chemokines. (Blood. 2000;95:1167-1174)
Annunziato
F
F
Department of Internal Medicine, Section of Immunoallergology and Respiratory Disorders, University of Florence, Florence, Italy.
Galli
G
G
Nappi
F
F
Cosmi
L
L
Manetti
R
R
Maggi
E
E
Ensoli
B
B
Romagnani
S
S
D000328:Adult; D016764:Cell Polarity; D002478:Cells, Cultured; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000096:biosynthesis*; D003881:Dermatomycoses / Q000097:blood / Q000276:immunology; D016655:HIV Core Protein p24 / Q000096:biosynthesis / Q000097:blood; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis*; D019713:Receptors, CCR5 / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000821:virology; D018417:Th1 Cells / Q000276:immunology / Q000821:virology; D018418:Th2 Cells / Q000276:immunology / Q000821:virology; D014779:Virus Replication
D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D016655:HIV Core Protein p24; D019402:Macrophage Inflammatory Proteins; D019713:Receptors, CCR5