Limited expression of R5-tropic HIV-1 in CCR5-positive type 1-polarized T cells explained by their ability to produce RANTES, MIP-1 alpha, and MIP-1 beta

Human T helper (ih) cells (Th1- or Th2-oriented memory T cells as well as T h1- or Th2-polarized naive T cells) were infected in vitro with an RS-tropi c HIV-1 strain (BaL) and assessed for their profile of cytokine production, CCR5 receptor expression, and HIV-1 p24 antigen (p24 Ag) production. Highe r 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 w as higher in Th1-polarized activated naive T cells in the first 4 days afte r infection. However, p24 Ag production in Th1-polarized T cells became com parable or even lower than the production in Th2-polarized populations late r in infection or when the cells were infected with HIV-1BaL after secondar y stimulation. The higher levels of p24 Ag production by Th1-polarized naiv e T cells soon after infection reflected a higher virus entry, as assessed by the single round infection assay using the HIV-chloramphenicol acetyl tr ansferase (HIV-CAT) RS-tropic virus that contains the envelope protein of H IV-I YU2 strain. The limitation of viral spread in the Th1-polarized popula tions, despite the initial higher level of T-cell entry of RS-tropic strain s, was due to the ability of Th1 cells to produce greater amounts of beta-c hemokines than Th2 cells. In fact, an inverse correlation was observed betw een Th1-polarized naive T cells and Th1-like memory-activated T cells in re gards to p24 Ag production and the release of the following CCR5-binding ch emokines: regulated on activation normal T expressed and secreted (RANTES), macrophage inflammatory protein-1 alpha (MIP-1 alpha), and MIP-1 beta, Mor eover, infection with the HIV-1 Bat strain of Th1-polarized T cells in the presence of a mixture of anti-RANTES, anti-MIP-1 alpha, and anti-MIP-1 beta neutralizing antibodies resulted in a significant increase of HIV-1 expres sion. These findings suggest that Th1-type responses may favor CD4(+) T-cel l infection by RS-tropic HIV-1 strains, but HIV-1 spread in Th1 cells is li mited by their ability to produce CCR5-binding chemokines.