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IL-10 down-regulates costimulatory molecules onMycobacterium tuberculosis-pulsed macrophages and impairs the lytic activity of CD4 and CD8 CTL in tuberculosis patients.
- Source :
- Clinical & Experimental Immunology; Oct2004, Vol. 138 Issue 1, p128-138, 11p
- Publication Year :
- 2004
-
Abstract
- Activation of T cells requires both TCR-specific ligation and costimulation through accessory molecules during T cell priming. IFNγ is a key cytokine responsible for macrophage activation duringMycobacterium tuberculosis(Mtb) infection while IL-10 is associated with suppression of cell mediated immunity in intracellular infection. In this paper we evaluated the role of IFNγ and IL-10 on the function of cytotoxic T cells (CTL) and on the modulation of costimulatory molecules in healthy controls and patients with active tuberculosis (TB).γ-irradiated-Mtb(i-Mtb) induced IL-10 production from CD14<superscript>+</superscript> cells from TB patients. Moreover, CD3<superscript>+</superscript> T cells of patients with advanced disease also produced IL-10 after i-Mtbstimulation. In healthy donors, IL-10 decreased the lytic activity of CD4<superscript>+</superscript> and CD8<superscript>+</superscript> T cells whereas it increasedγδ-mediated cytotoxicity. Furthermore, we found that the presence of IL-10 induced a loss of the alternative processing pathways of antigen presentation along with a down-regulation of the expression of costimulatory molecule expression on monocytes and macrophages from healthy individuals. Conversely, neutralization of endogenous IL-10 or addition of IFNγ to either effector or target cells from TB patients induced a strong lytic activity mediated by CD8<superscript>+</superscript> CTL together with an up-regulation of CD54 and CD86 expression on target cells. Moreover, we observed that macrophages from TB patients could use alternative pathways for i-Mtbpresentation. Taken together, our results demonstrate that the presence of IL-10 duringMtbinfection might contribute to mycobacteria persistence inside host macrophages through a mechanism that involved inhibition of MHC-restricted cytotoxicity against infected macrophages. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00099104
- Volume :
- 138
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- Clinical & Experimental Immunology
- Publication Type :
- Academic Journal
- Accession number :
- 14418413
- Full Text :
- https://doi.org/10.1111/j.1365-2249.2004.02577.x