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Blood, Vol. 95 No. 4 (February 15), 2000:
pp. 1167-1174
Limited expression of R5-tropic HIV-1 in CCR5-positive type
1-polarized T cells explained by their ability to produce RANTES,
MIP-1 , and MIP-1
Francesco Annunziato,
Grazia Galli,
Filomena Nappi,
Lorenzo Cosmi,
Roberto Manetti,
Enrico Maggi,
Barbara Ensoli, and
Sergio Romagnani
From the Department of Internal Medicine, Section of
Immunoallergology and Respiratory Disorders, University of Florence,
Florence, Italy, and the Laboratory of Virology, Superior Institute of
Health, Rome, Italy.
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  -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-1 (MIP-1), and MIP-1. Moreover,
infection with the HIV-1BaL strain of Th1-polarized T cells in the
presence of a mixture of anti-RANTES, anti-MIP-1, and
anti-MIP-1 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.
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