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Regulatory T cells are expanded in blood and disease sites in patients with tuberculosis

Regulatory T cells are expanded in blood and disease sites in patients with tuberculosis
Regulatory T cells are expanded in blood and disease sites in patients with tuberculosis
Rationale: T-cell responses during tuberculosis (TB) help contain Mycobacterium tuberculosis in vivo but also cause collateral damage to host tissues. Immune regulatory mechanisms may limit this immunopathology, and suppressed cellular immune responses in patients with TB suggest the presence of regulatory activity. CD4+CD25high regulatory T cells mediate suppressed cellular immunity in several chronic infections but have not been described in TB.

Objective: To determine whether regulatory T cells are increased in patients with TB and whether they suppress cellular immune responses.

Methods: We compared the frequency of circulating regulatory T cells in 27 untreated patients with TB and 23 healthy control subjects using two specific markers: cell-surface CD25 expression and FoxP3 mRNA expression in peripheral blood mononuclear cells.

Measurements and Main Results: We detected a threefold increase in the frequency of CD4+CD25high T cells (p < 0.001) and a 2.2-fold increase in FoxP3 expression (p = 0.006) in patients with TB, and there was a positive correlation between these markers (r = 0.58, p < 0.001). Increased expression of interleukin-10 and transforming growth factor-beta1 mRNA was also detected in patients with TB but did not correlate with regulatory T-cell markers. Ex vivo depletion of CD4+CD25high cells from peripheral blood mononuclear cells resulted in increased numbers of M. tuberculosis antigen–specific IFN-{gamma}–producing T cells in seven of eight patients with TB (p = 0.005). Finally, FoxP3 expression was increased 2.3-fold in patients with extrapulmonary TB compared with patients with purely pulmonary TB (p = 0.01) and was amplified 2.6-fold at disease sites relative to blood (p = 0.043).

Conclusions: Regulatory T cells are expanded in patients with TB and may contribute to suppression of Th1-type immune responses.
CD4+, CD25+, regulatory t cells, foxP3, immunopathology, mycobacterium tuberculosis
1073-449X
803-810
Guyot-Revol, Valerie
41945b51-2e48-4ac4-9529-fb389daa2b8c
Innes, John A.
1ec06c23-0edc-4c17-bd6a-2a2e88132c4c
Hackforth, Sarah
8c13ee82-2042-400f-8e70-38f609cf0831
Hinks, Tim
7117a072-2b0a-4012-a4b5-2f70ac54711c
Lalvani, Ajit
ac754f14-ec6b-4a5b-8a72-6bb1e114b626
Guyot-Revol, Valerie
41945b51-2e48-4ac4-9529-fb389daa2b8c
Innes, John A.
1ec06c23-0edc-4c17-bd6a-2a2e88132c4c
Hackforth, Sarah
8c13ee82-2042-400f-8e70-38f609cf0831
Hinks, Tim
7117a072-2b0a-4012-a4b5-2f70ac54711c
Lalvani, Ajit
ac754f14-ec6b-4a5b-8a72-6bb1e114b626

Guyot-Revol, Valerie, Innes, John A., Hackforth, Sarah, Hinks, Tim and Lalvani, Ajit (2006) Regulatory T cells are expanded in blood and disease sites in patients with tuberculosis. American Journal of Respiratory and Critical Care Medicine, 173 (7), 803-810. (doi:10.1164/rccm.200508-1294OC). (PMID:16339919)

Record type: Article

Abstract

Rationale: T-cell responses during tuberculosis (TB) help contain Mycobacterium tuberculosis in vivo but also cause collateral damage to host tissues. Immune regulatory mechanisms may limit this immunopathology, and suppressed cellular immune responses in patients with TB suggest the presence of regulatory activity. CD4+CD25high regulatory T cells mediate suppressed cellular immunity in several chronic infections but have not been described in TB.

Objective: To determine whether regulatory T cells are increased in patients with TB and whether they suppress cellular immune responses.

Methods: We compared the frequency of circulating regulatory T cells in 27 untreated patients with TB and 23 healthy control subjects using two specific markers: cell-surface CD25 expression and FoxP3 mRNA expression in peripheral blood mononuclear cells.

Measurements and Main Results: We detected a threefold increase in the frequency of CD4+CD25high T cells (p < 0.001) and a 2.2-fold increase in FoxP3 expression (p = 0.006) in patients with TB, and there was a positive correlation between these markers (r = 0.58, p < 0.001). Increased expression of interleukin-10 and transforming growth factor-beta1 mRNA was also detected in patients with TB but did not correlate with regulatory T-cell markers. Ex vivo depletion of CD4+CD25high cells from peripheral blood mononuclear cells resulted in increased numbers of M. tuberculosis antigen–specific IFN-{gamma}–producing T cells in seven of eight patients with TB (p = 0.005). Finally, FoxP3 expression was increased 2.3-fold in patients with extrapulmonary TB compared with patients with purely pulmonary TB (p = 0.01) and was amplified 2.6-fold at disease sites relative to blood (p = 0.043).

Conclusions: Regulatory T cells are expanded in patients with TB and may contribute to suppression of Th1-type immune responses.

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More information

Published date: 1 April 2006
Keywords: CD4+, CD25+, regulatory t cells, foxP3, immunopathology, mycobacterium tuberculosis

Identifiers

Local EPrints ID: 171993
URI: http://eprints.soton.ac.uk/id/eprint/171993
ISSN: 1073-449X
PURE UUID: a437e656-e673-49d3-9fc8-d924e4bec001

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Date deposited: 27 Jan 2011 14:49
Last modified: 14 Mar 2024 02:27

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Contributors

Author: Valerie Guyot-Revol
Author: John A. Innes
Author: Sarah Hackforth
Author: Tim Hinks
Author: Ajit Lalvani

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