Impaired mononuclear-cell proliferation in patients with the acquired immune deficiency syndrome results from abnormalities of both T lymphocytes and adherent mononuclear cells

Abstract

Peripheral blood mononuclear cells from patients with acquired immune deficiency syndrome proliferate poorly after stimulation with soluble mitogens. The present study was undertaken to assess the relative contributions of T lymphocytes and of plastic adherent mononuclear cells to the impaired mononuclear cell responses. We employed a four-step separation procedure including terminal depletion using a monocyte-specific monoclonal antibody (61D3) to derive populations of highly purified T cells from patients and from normal subjects. Highly purified T cells proliferated poorly in response to phytohemagglutinin and pokeweed mitogen. The addition of autologous adherent cells to highly purified T cells markedly improved mitogen-driven proliferation in all subjects; however, mononuclear cells from patients with AIDS responded less well than normals (P≦0.01) for both phytohemagglutinin and pokeweed. Allogeneic normal adherent cells fully restored both phytohemagglutinin and pokeweed responses in normal highly purified T cells. Adherent cells from patients were comparable to normal adherent cells in phytohemagglutinin-driven proliferation but performed significantly less well when pokeweed was used to stimulate normal highly purified T-cell responders (4308 cpm after coculture with patients' adherent cells vs 8244 cpm after coculture with allogeneic normal adherent cells;P=0.05). Similarly, when patient's highly purified T cells were stimulated with pokeweed mitogen, control adherent cells functioned substantially better than patient adherent cells (1198 cpm for allogeneic patient adherent cells vs 2324 cpm for normal adherent cells;P=0.05). Although the addition of normal adherent cells to patients' highly purified T cells significantly improved pokeweed mitogen responses, these values did not reach normal. Suppression by patients adherent cells was not demonstrated. Abnormal mitogen responses in acquired immunodeficiency appear to be primarily a result of an intrinsic T-lymphocyte disorder. This defect cannot be correctedin vitro by coculture with normal adherent cells. Adherent mononuclear cells from patients with acquired immunodeficiency supported phytohemagglutinin responses as well as normal adherent cells. However, patients' adherent cells showed decreased accessory function when pokeweed mitogen was employed to stimulate responder cells. These data suggest that abnormalities of adherent mononuclear cells are present in patients with acquired immunodeficiency and that this defect may contribute to the impaired mitogen responses in these patients. Pokeweed mitogen assays are particularly sensitive in demonstrating abnormal accessory-cell function.