Reduced production of interleukin 2 and interferongamma and enhanced helper activity for IgG synthesis by cloned CD4+ T cells from patients with AIDS

Abstract

Purified T lymphocytes (E rosetting cells) isolated from peripheral blood (PB) of four patients with acquired immune deficiency syndrome (AIDS) were cloned under culture conditions (phytohemagglutinin plus interleukin 2) which allow clonal expansion of most T lymphocytes. A total number of 101 T cell clones (37 CD4⁺ and 64 CD8⁺) from PB of AIDS patients and of 188 T cell clones (115 CD4⁺ and 73 CD8⁺) from PB of four normal controls were obtained and tested for their helper function as well as for their capacity to release lymphokines. Unstimulated CD4⁺ TCC from patients with AIDS showed enhanced helper function for IgG synthesis in vitro in both autologous and normal allogeneic B cells in comparison to clonable CD4⁺ T cells of normal donors. Such activity was further potentiated by addition to the cell cultures of anti-CD3 monoclonal antibody. The majority of CD4⁺ T cell clones from AIDS patients showed a reduced ability to produce interleukin 2 and interferon-γ in response to activation with phytohemagglutinin. However, most of them released greater amounts of soluble factor(s) able to promote B cell proliferation of anti-IgM-activated normal B cells and to induce the differentiation of normal B lymphocytes into IgG-secreting cells. These data demonstrate that most surviving CD4⁺ T cells in PB of patients with AIDS belong to a T cell subset producing B cell growth and differentiation factors, which may contribute to the B cell hyperactivation seen in AIDS patients.