IL-10 down-regulates costimulatory molecules on Mycobacterium tuberculosis-pulsed macrophages and impairs the lytic activity of CD4 and CD8 CTL in tuberculosis patients

Clin Exp Immunol. 2004 Oct;138(1):128-38. doi: 10.1111/j.1365-2249.2004.02577.x.


Activation of T cells requires both TCR-specific ligation and costimulation through accessory molecules during T cell priming. IFNgamma is a key cytokine responsible for macrophage activation during Mycobacterium 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 IFNgamma 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). gamma-irradiated-Mtb (i-Mtb) induced IL-10 production from CD14(+) cells from TB patients. Moreover, CD3(+) T cells of patients with advanced disease also produced IL-10 after i-Mtb stimulation. In healthy donors, IL-10 decreased the lytic activity of CD4(+) and CD8(+) T cells whereas it increased gammadelta-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 IFNgamma to either effector or target cells from TB patients induced a strong lytic activity mediated by CD8(+) 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-Mtb presentation. Taken together, our results demonstrate that the presence of IL-10 during Mtb infection might contribute to mycobacteria persistence inside host macrophages through a mechanism that involved inhibition of MHC-restricted cytotoxicity against infected macrophages.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antigen Presentation / immunology
  • Antigens, CD / immunology
  • B7-2 Antigen
  • CD3 Complex / immunology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD40 Antigens / immunology
  • Humans
  • Intercellular Adhesion Molecule-1 / immunology
  • Interferon-gamma / immunology
  • Interleukin-10
  • Leukocytes, Mononuclear / immunology
  • Lipopolysaccharide Receptors / immunology
  • Lymphocyte Activation / immunology
  • Macrophages / immunology*
  • Membrane Glycoproteins / immunology
  • Middle Aged
  • Mycobacterium tuberculosis / immunology*
  • T-Lymphocytes, Cytotoxic / immunology*
  • Tuberculosis, Pulmonary / immunology*


  • Antigens, CD
  • B7-2 Antigen
  • CD3 Complex
  • CD40 Antigens
  • CD86 protein, human
  • Lipopolysaccharide Receptors
  • Membrane Glycoproteins
  • Intercellular Adhesion Molecule-1
  • Interleukin-10
  • Interferon-gamma