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T cell-derived IL-10 antagonizes macrophage function in mycobacterial infection
P J Murray1, L Wang, C Onufryk
1Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Journal of Immunology (Baltimore, Md. : 1950)
|January 1, 1997
Summary
Interleukin-10 (IL-10) impairs macrophage anti-mycobacterial activity, prolonging infections. This study shows IL-10 primarily affects macrophages, not T cells, during mycobacterial infections.
Area of Science:
- Immunology
- Microbiology
Background:
- Pathogenic mycobacteria evade macrophage defenses, aided by T cell-derived cytokines like IL-10.
- IL-10 negatively regulates Th1 cells and macrophages, inhibiting anti-mycobacterial activity in vitro.
Purpose of the Study:
- To investigate the in vivo role of T cell-derived IL-10 in controlling mycobacterial infections.
- To determine if IL-10 impacts T cell function or macrophage activity during infection.
Main Methods:
- Generation of transgenic mice secreting IL-10 from T cells.
- Infection of these mice with Mycobacterium bovis (Calmette-Guérin bacillus).
- Assessment of bacterial burden and T cell cytokine production (IFN-gamma, IL-2) upon antigen challenge.
Main Results:
- Transgenic mice exhibited impaired infection clearance and increased bacterial loads.
- T cells from these mice produced robust IFN-gamma and IL-2, indicating preserved T cell function.
- IL-10 did not significantly affect T cell responses to the bacteria.
Conclusions:
- Excess IL-10, even when T cell-derived, does not impede T cell responses against mycobacteria.
- IL-10 contributes to persistent mycobacterial infections by inhibiting macrophage anti-mycobacterial functions, overriding IFN-gamma signaling.