Effects of systemic in vivo interleukin-2 (IL-2) reconstitution in patients with acquired immune deficiency syndrome (AIDS) and AIDS-related complex (ARC) on phenotypes and functions of peripheral blood mononuclear cells (PBMC)

Abstract

In the context of a clinical phase I/II therapy study with recombinant interleukin-2 (rIL-2), we monitored immunological alterations in four patients with acquired immune deficiency syndrome (AIDS) and three patients with AIDS-related complex (ARC). By determining the surface phenotypes and in vitro functions of peripheral blood mononuclear cells (PBMC) before, during, and after treatment with rIL-2, we observed transient changes in all important leukocyte subpopulations, a minor restoration of immune reactivity in vitro, and an improvement in skin reactivity in vivo. In particular, we found a transient increase in C3b receptor-mediated monocyte activation in ARC patients; no influence of therapy on the otherwise intact LPS-induced interleukin-1 production in vitro; in some patients a transient corrective influence on the high pretherapeutic immunoglobulin secretion of B cells and their nonresponsiveness to pokeweed mitogen; low T-cell responses to soluble antigens and alloantigens, which were partially restored during rIL-2 treatment in ARC patients and in one AIDS patient; defective NK activity in PBMC of two AIDS patients, which was found to be restored when measured at the end of rIL-2 therapy; and a rather constant phenotypic pattern of PBMC in each patient during therapy except for the decreasing proportion of OKT9-positive lymphocytes in AIDS patients, the increasing proportion of Leu8-Leu3a+ lymphocytes in all patients, and in particular, the transient significant decrease in the Leu7+/OKT3+ ratio, which pretherapeutically was very high in AIDS patients (0.78 +/- 0.21) and high in ARC patients (0.48 +/- 0.06) as compared to healthy controls (0.18 +/- 0.08).