Affiliation:
1. Department of Medicine, Case Western Reserve University and University Hospitals of Cleveland, Cleveland, Ohio 44106-4984
Abstract
ABSTRACT
Mycobacterium tuberculosis
is the etiologic agent of human tuberculosis and is estimated to infect one-third of the world's population. Control of
M. tuberculosis
requires T cells and macrophages. T-cell function is modulated by the cytokine environment, which in mycobacterial infection is a balance of proinflammatory (interleukin-1 [IL-1], IL-6, IL-8, IL-12, and tumor necrosis factor alpha) and inhibitory (IL-10 and transforming growth factor β [TGF-β]) cytokines. IL-10 and TGF-β are produced by
M. tuberculosis
-infected macrophages. The effect of IL-10 and TGF-β on
M. tuberculosis
-reactive human CD4
+
and γδ T cells, the two major human T-cell subsets activated by
M. tuberculosis
, was investigated. Both IL-10 and TGF-β inhibited proliferation and gamma interferon production by CD4
+
and γδ T cells. IL-10 was a more potent inhibitor than TGF-β for both T-cell subsets. Combinations of IL-10 and TGF-β did not result in additive or synergistic inhibition. IL-10 inhibited γδ and CD4
+
T cells directly and inhibited monocyte antigen-presenting cell (APC) function for CD4
+
T cells and, to a lesser extent, for γδ T cells. TGF-β inhibited both CD4
+
and γδ T cells directly and had little effect on APC function for γδ and CD4
+
T cells. IL-10 down-regulated major histocompatibility complex (MHC) class I, MHC class II, CD40, B7-1, and B7-2 expression on
M. tuberculosis
-infected monocytes to a greater extent than TGF-β. Neither cytokine affected the uptake of
M. tuberculosis
by monocytes. Thus, IL-10 and TGF-β both inhibited CD4
+
and γδ T cells but differed in the mechanism used to inhibit T-cell responses to
M. tuberculosis
.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology
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