title: 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.
abstract: The loss of immune function following infection with human immunodeficiency virus (HIV) may result from altered production of immunoregulatory cytokines such as interleukin-10 (IL-10) and IL-12. In this study, we analyzed IL-10 and IL-12 production by mitogen-stimulated peripheral blood mononuclear cells (PBMC) from HIV+ individuals and correlated their levels with proliferative responses to the recall antigens HIV p25 and influenza virus. We report two distinct groups of HIV+ patients. One group produced small amounts of IL-10, had PBMC that proliferated in response to recall antigens, and demonstrated enhanced recall antigen-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 demonstrate enhanced proliferation upon addition of anti-IL-10 antibodies and/or IL-12. Mitogen-stimulated PBMC from both groups produced significantly lower levels of IL-12 than did those from HIV- controls. Analysis of the source of the IL-10-producing cell subset in PBMC demonstrated 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 secrete decreased amounts of IL-12, a Th1-type cytokine, which may lead to the development of Th2-type responses characterized by high IL-10 secretion and immune dysfunction.
authors.affiliation: Department of Pediatrics, Children's Hospital of Eastern Ontario, University of Ottawa, Canada.
authors.forename: M P
authors.initials: MP
authors.lastname: Daftarian
authors.forename: F
authors.initials: F
authors.lastname: Diaz-Mitoma
authors.forename: W D
authors.initials: WD
authors.lastname: Creery
authors.forename: W
authors.initials: W
authors.lastname: Cameron
authors.forename: A
authors.initials: A
authors.lastname: Kumar
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000378:metabolism; D000328:Adult; D000956:Antigens, Viral / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D000090266:Chromobox Protein Homolog 5; D015488:HIV Antigens / Q000378:metabolism; D006801:Humans; D007156:Immunologic Memory; D016753:Interleukin-10 / Q000096:biosynthesis*; D018664:Interleukin-12 / Q000096:biosynthesis*; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology; D008934:Mitogens / Q000494:pharmacology; D010835:Phytohemagglutinins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000378:metabolism*
chemical_list: D000956:Antigens, Viral; C000715594:CBX5 protein, human; D015488:HIV Antigens; D008934:Mitogens; D010835:Phytohemagglutinins; D000090266:Chromobox Protein Homolog 5; D016753:Interleukin-10; D018664:Interleukin-12