Experiences in immune reconstitution. The rationale for interleukin-2 administration to HIV-infected individuals

Since the clinical earliest descriptions of patients with acquired immune deficiency syndrome (AIDS) it has been very clear that a profound state of immunologic dysfunction was the underlying cause of the emergence of life-threatening opportunistic infections and tumors. In addition to the progressive loss of CD4 ''helper'' T lymphocytes, a profound defect in interleukin-2 (IL-2) production was recognized as a major pathogenic component of the new disease. For these reasons, attempts to administer IL-2 to individuals infected with the human immunodeficiency virus (HIV), the causative agent of AIDS, have been made since the mid eighties, however with little success. On the other hand the propensity of HIV to replicate in activated lymphocytes and macrophages, under the influence of cytokine network, has represented, and in part still does, a major hurdle for the rationale of administrating IL-2 or other cytokines to HIV-infected individuals. Major steps forward towards an understanding of the role of multiple components of the immune system, coupled with a potentially successful protocol of IL-2 administration in vivo, resulting in the stable uprising of circulating CD4+ T cells, shed an optimistic light on the possibility to achieve a substantial immune reconstitution in HIV-infected individuals, thus preventing the onset of AIDS.