NK1.1(+) Cells and IL-22 Regulate Vaccine-Induced Protective Immunity against Challenge with Mycobacterium tuberculosis

作者：Dhiman Rohan; Periasamy Sivakumar; Barnes Peter F; Jaiswal Ankita Garg; Paidipally Padmaja; Barnes Amanda B; Tvinnereim Amy; Vankayalapati Ramakrishna^*

来源：The Journal of Immunology, 2012, 189(2): 897-905.

DOI：10.4049/jimmunol.1102833

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-Guerin ( BCG), followed by challenge with virulent M. tuberculosis H37Rv. BCG vaccination enhanced the number of IFN-gamma-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. The Journal of Immunology, 2012, 189: 897-905.

• 出版日期2012-7-15