DYSREGULATED PRODUCTION OF INTERLEUKIN-10 (IL-10) AND IL-12 BY PERIPHERAL-BLOOD LYMPHOCYTES FROM HUMAN IMMUNODEFICIENCY VIRUS-INFECTED INDIVIDUALS IS ASSOCIATED WITH ALTERED PROLIFERATIVE RESPONSES TO RECALL ANTIGENS

The loss of immune function following infection with human immunodefic iency virus (HIV) may result from altered production of immunoregulato ry cytokines such as interleukin-10 (IL-10) and IL-12. In this study, we analyzed IL-10 and IL-12 production by mitogen-stimulated periphera l blood mononuclear cells (PBMC) from HIV+ individuals and correlated their levels with proliferative responses to the recall antigens HIV p 25 and influenza virus. We report two distinct groups of HIV+ patients . One group produced small amounts of IL-10, had PBMC that proliferate d in response to recall antigens, and demonstrated enhanced recall ant igen-induced proliferation upon addition of anti-IL-10 antibodies and/ or IL-12. Conversely, the second group produced high levels of IL-10, had PBMC that failed to proliferate to recall antigens, and did not de monstrate enhanced proliferation upon addition of anti-IL-10 antibodie s and/or IL-12. Mitogen-stimulated PBMC from both groups produced sign ificantly lower levels of IL-12 than did those from HIV- controls. Ana lysis of the source of the IL-10-producing cell subset in PBMC demonst rated that in HIV+ individuals, IL-10 is produced by monocytes, while in HIV- controls, it is produced by both T cells and monocytes. Taken together, our results suggest that monocytes from HIV+ individuals sec rete decreased amounts of IL-12, a Th1-type cytokine, which may lead t o the development of Th2-type responses characterized by high IL-10 se cretion and immune dysfunction.