title: Interleukin-4 and interferon-gamma production by Leishmania stimulated peripheral blood mononuclear cells from nonexposed individuals.
abstract: Interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) production by Leishmania reactive peripheral blood mononuclear cells (PBMC) from non-exposed individuals was investigated. IFN-gamma was measured in culture supernatants after antigen stimulation. For the measurement of IL-4, antigen stimulated cells were pulsed with PMA and ionomycin before IL-4 release was measured. L. donovani and L. major antigens induced IL-4 production (105-1748 pg/ml) in 13 and seven cultures, and IFN-gamma production (1.7 - > 66 IU/ml) in 14 and 11 of 20 cultures, respectively. IL-4 production rose steeply after 6 days of antigen stimulation suggesting a response due to antigen recognition. Both IL-4 and IFN-gamma production was abrogated by depletion of CD2+ or CD4+ but not CD8+ cells. CD2+ or CD4+ but not CD8+ enriched cultures produced cytokines as unseparated PBMC. Thus, in non-exposed individuals circulating Leishmania reactive CD4+ T cells could be demonstrated. The cells from different individuals showed different patterns of IFN-gamma and/or IL-4 production upon antigenic stimulation. In experimental leishmaniasis the early balance between IFN-gamma and IL-4 is important for the clinical outcome. Our findings call for studies of the importance of cytokine production by cross-reactive T cells for the outcome of L. donovani infections in humans and show that the method for IL-4 detection is useful for this purpose.
authors.affiliation: Centre for Medical Parasitology, University of Copenhagen, Denmark.
authors.forename: J A
authors.initials: JA
authors.lastname: Kurtzhals
authors.forename: M
authors.initials: M
authors.lastname: Kemp
authors.forename: L K
authors.initials: LK
authors.lastname: Poulsen
authors.forename: M B
authors.initials: MB
authors.lastname: Hansen
authors.forename: A
authors.initials: A
authors.lastname: Kharazmi
authors.forename: T G
authors.initials: TG
authors.lastname: Theander
mesh_terms: D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology*; D018801:CD2 Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D003470:Culture Media; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000096:biosynthesis*; D007893:Leishmania donovani / Q000276:immunology*; D018320:Leishmania major / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008213:Lymphocyte Activation
chemical_list: D000953:Antigens, Protozoan; D018801:CD2 Antigens; D003470:Culture Media; D015847:Interleukin-4; D007371:Interferon-gamma