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NK Cells Lyse T Regulatory Cells That Expand in Response to an Intracellular Pathogen

Sugata Roy, Peter F. Barnes, Ankita Garg, Shiping Wu, David Cosman and Ramakrishna Vankayalapati
J Immunol February 1, 2008, 180 (3) 1729-1736; DOI: https://doi.org/10.4049/jimmunol.180.3.1729
Sugata Roy
*Center for Pulmonary and Infectious Disease Control,
†Departments of Microbiology and Immunology and
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Peter F. Barnes
*Center for Pulmonary and Infectious Disease Control,
†Departments of Microbiology and Immunology and
‡Department of Medicine, University of Texas Health Center, Tyler, TX 75708l; and
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Ankita Garg
*Center for Pulmonary and Infectious Disease Control,
†Departments of Microbiology and Immunology and
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Shiping Wu
*Center for Pulmonary and Infectious Disease Control,
†Departments of Microbiology and Immunology and
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David Cosman
§Amgen, Seattle, WA 98101
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Ramakrishna Vankayalapati
*Center for Pulmonary and Infectious Disease Control,
†Departments of Microbiology and Immunology and
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Abstract

We evaluated the capacity of NK cells to influence expansion of CD4+CD25+FoxP3+ regulatory T cells (Tregs) in response to microbial Ags, using Mycobacterium tuberculosis as a model. We previously found that Tregs expand when CD4+ cells and monocytes are exposed to M. tuberculosis. Addition of NK cells that were activated by monokines (IL-12, IL-15, and IL-18) or by exposure to M. tuberculosis-stimulated monocytes reduced Treg expansion in response to M. tuberculosis. NK cell inhibition of Treg expansion was not mediated through IFN-γ. Activated NK cells lysed expanded, but not freshly isolated Tregs. Although monokines increased NK cell expression of the activating receptors NKp46, NKG2D, 2B4, CD16, and DNAM-1, only anti-NKG2D and anti-NKp46 inhibited NK cell lysis of expanded Tregs. Of five NKG2D ligands, only UL16-binding protein 1 (ULBP1) was up-regulated on M. tuberculosis-expanded Tregs, and anti-ULBP1 inhibited NK cell lysis of expanded Tregs. M. tuberculosis-stimulated monocytes activated NK cells to lyse expanded Tregs, and this was also inhibited by anti-NKG2D and anti-ULBP1, confirming the physiological relevance of this effect. Our study identifies a potential new role for NK cells in maintaining the delicate balance between the regulatory and effector arms of the immune response.

  • Received April 26, 2007.
  • Accepted November 25, 2007.
  • Copyright © 2008 by The American Association of Immunologists
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The Journal of Immunology: 180 (3)
The Journal of Immunology
Vol. 180, Issue 3
1 Feb 2008
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NK Cells Lyse T Regulatory Cells That Expand in Response to an Intracellular Pathogen
Sugata Roy, Peter F. Barnes, Ankita Garg, Shiping Wu, David Cosman, Ramakrishna Vankayalapati
The Journal of Immunology February 1, 2008, 180 (3) 1729-1736; DOI: 10.4049/jimmunol.180.3.1729

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NK Cells Lyse T Regulatory Cells That Expand in Response to an Intracellular Pathogen
Sugata Roy, Peter F. Barnes, Ankita Garg, Shiping Wu, David Cosman, Ramakrishna Vankayalapati
The Journal of Immunology February 1, 2008, 180 (3) 1729-1736; DOI: 10.4049/jimmunol.180.3.1729
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