NK1. 1+ cells and IL-22 regulate vaccine-induced protective immunity against challenge with Mycobacterium tuberculosis

R Dhiman, S Periasamy, PF Barnes… - The Journal of …, 2012 - journals.aai.org
R Dhiman, S Periasamy, PF Barnes, AG Jaiswal, P Paidipally, AB Barnes, A Tvinnereim…
The Journal of Immunology, 2012journals.aai.org
We previously found that human NK cells lyse Mycobacterium tuberculosis-infected
monocytes and alveolar macrophages and upregulate CD8+ T cell responses. We also
found that human NK cells produce IL-22, which inhibits intracellular growth of M.
tuberculosis, and that NK cells lyse M. tuberculosis-expanded CD4+ CD25+ FOXP3+ T
regulatory cells (Tregs). To determine the role of NK cells during the protective immune
response to vaccination in vivo, we studied the NK cell and T cell responses in a mouse …
Abstract
We previously found that human NK cells lyse Mycobacterium tuberculosis-infected monocytes and alveolar macrophages and upregulate CD8+ T cell responses. We also found that human NK cells produce IL-22, which inhibits intracellular growth of M. tuberculosis, and that NK cells lyse M. tuberculosis-expanded CD4+ CD25+ FOXP3+ T regulatory cells (Tregs). To determine the role of NK cells during the protective immune response to vaccination in vivo, we studied the NK cell and T cell responses in a mouse model of vaccination with bacillus Calmette-Guérin (BCG), followed by challenge with virulent M. tuberculosis H37Rv. BCG vaccination enhanced the number of IFN-γ–producing and IL-22–producing NK cells. Depletion of NK1. 1+ cells at the time of BCG vaccination increased the number of immunosuppressive Tregs (CD4+ CD25 hi, 95% Foxp3+) after challenge with M. tuberculosis H37Rv, and NK1. 1+ cells lysed expanded but not natural Tregs in BCG-vaccinated mice. Depletion of NK1. 1+ cells at the time of BCG vaccination also increased the bacillary burden and reduced T cell responses after challenge with M. tuberculosis H37Rv. IL-22 at the time of vaccination reversed these effects and enhanced Ag-specific CD4+ cell responses in BCG-vaccinated mice after challenge with M. tuberculosis H37Rv. Our study provides evidence that NK1. 1+ cells and IL-22 contribute to the efficacy of vaccination against microbial challenge.
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