Human immunodeficiency virus-1 infection protects against a Tc1-to-Tc2 shift in CD8+ T cells

Despite the reports of dysfunction of the lytic abilities of CD8+ T cells during human immunodeficiency virus-1 (HIV-1) disease progression, the effects of infection on the noncytolytic functions of CD8+ T cells have not been well characterized to date. We examined the effect of HIV-1 infection on the cytokine and chemokine responses of peripheral blood–derived CD8+ T cells in an in vitro system. Activation of HIV-1-infected CD8+ T cells with phytohemagglutinin resulted in a 4- to 8-fold increase in the production of macrophage inflammatory protein (MIP)-1α, MIP-1β, regulated on activation normal T-cell expressed and secreted, and interleukin (IL)-16. Treatment of activated HIV-1-infected CD8+ T cells with anti-CD3 monoclonal (M) antibody (Ab) and IL-15 induced strong production of interferon-γ (IFN-γ). Treatment of cells with anti-IL-12 MAb and IL-4 to induce a Tc1-to-Tc2 shift resulted in no change in viral production levels or IFN-γ production within the HIV-1-infected CD8+ T cell population. Initiation of a Tc2-to-Tc1 shift resulted in a 6-fold increase in HIV-1 replication and 2- to 3-fold higher levels of IFN-γ, demonstrating that infection can protect against a Tc1-to-Tc2 shift in CD8+ T cells.