Interleukin-4 and Interferon-Gamma Production by Leishmania Stimulated Peripheral Blood Mononuclear Cells from Nonexposed Individuals |
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Authors: | J A L KURTZHALS† M KEMP‡ L K POULSEN§ M B HANSEN† A KHARAZMI¶ T G THEANDER‡ |
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Institution: | Centre for Medical Parasitotagy, University of Copenhagen, Copenhagen. Denmark;Department of Infectious Diseases, National University Hospital, Copenhagen. Denmark;Department of Clinical Microbiology, National University Hospital, Copenhagen, Denmark;Laboratory of Medical Allergology, Department of Internal Medicine TTA, National University Hospital, Copenhagen, Denmark;Institute for Medical Microbiology and Immunology, University of Copenhagen, Copenhagen, Denmark |
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Abstract: | Interferon-gamma (IFN-γ) and interleukin-4 (IL-4) production by Leishmania reactive peripheral blood mononuclear cells (PBMC) from non-exposed individuals was investigated. IFN-γ 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 (105–1748pg/ml) in 13 and seven cultures, and IFN-γ production (1.7- > 66IU/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-γ 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-γ and/or IL-4 production upon antigenic stimulation. In experimental leishmaniasis the early balance between IFN-γ 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. |
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