Effects of Adoptive Immunotherapy with Autologous CD8 + T Lymphocytes on Immunologic Parameters: Lymphocyte Subsets and Cytotoxic Activity

CD8 + cytotoxic T lymphocytes (CTL) may be an important parameter of host resistance to HIV infection. The present study determined whether CD8 + cells could be purified and propagated in vitro to enhance anti-HIV CTL activity, and the immunologic effects of infusion of these cells into autologous, HIV-infected patients as a potential immunotherapy for AIDS and AIDS-related complex (ARC). CD8 + lymphocytes from five AIDS and ARC patients were purified from leukapheresis preparations in cell culture flasks coated with CD8-specific monoclonal antibodies and propagated in vitro for 3 weeks. The ex vivo propagated cells were 98% (±1%) CD8 + and 43% (±6%) HLA-DR +. The majority of the CD8 + cell preparations had increased lytic activity against autologous B lymphoblastoid cells infected with vaccinia virus vectors expressing HIV-IIIb structural proteins gag, pol, or env, relative to that of fresh blood mononuclear cells tested prior to purification and culture. The results also show for the first time that CD8 + CTL from HIV-infected patients can lyse cells expressing the HIV regulatory protein, tat. Enhanced expression of CD56 (natural killer cell marker) and lytic activity against vaccinia virus control vector-infected, autologous targets were also noted in the CD8 + cell preparations. Infusion of the CD8 + CTL into autologous patients was well-tolerated and resulted in low but discernible, temporal increases in circulating cytotoxic activity against the HIV gene-expressing targets.