A Subset of Mycobacteria-Specific CD4+ IFN-γ+ T Cell Expressing Naive Phenotype Confers Protection against Tuberculosis Infection in the Lung
Jinyun Yuan, Janice Tenant, Thomas Pacatte, Christopher S. Eickhoff, Azra Blazevic, Daniel F. Hoft, Soumya Chatterjee
The Journal of Immunology · 2019-06
Abstract
Abstract Failure of the most recent tuberculosis (TB) vaccine trial to boost bacillus Calmette–Guérin–mediated anti-TB immunity despite the induction of Th1-specific central memory cell and effector memory cell responses highlights the importance of identifying optimal T cell targets for protective vaccines. In this study, we describe a novel, Mycobacterium tuberculosis–specific IFN-γ+CD4+ T cell population expressing surface markers characteristic of naive-like memory T cells (TNLM), which were induced in both human (CD45RA+CCR7+CD27+CD95−) and murine (CD62L+CD44−Sca-1+CD122−) systems in response to mycobacteria. In bacillus Calmette–Guérin–vaccinated subjects and those with latent TB infection, TNLM were marked by the production of IFN-γ but not TNF-α and identified by the absence of CD95 expression and increased surface expression CCR7, CD27, the activation markers T-bet, CD69, and the survival marker CD74. Increased tetramer-positive TNLM frequencies were noted in the lung and spleen of ESAT-61–20–specific TCR transgenic mice at 2 wk postinfection with M. tuberculosis and progressively decreased at later time points, a pattern not seen with TNF-α+CD4+ T cells expressing naive cell surface markers. Importantly, adoptive transfer of highly purified TNLM alone, from vaccinated ESAT-61–20–specific TCR transgenic mice, conferred equivalent protection against M. tuberculosis infection in the lungs of Rag−/− mice when compared with total memory populations (central and effector memory cells). Thus, TNLM may represent a memory T cell population that, if optimally targeted, may significantly improve future TB vaccine responses.
MeSH terms
- Immunology
- Biology
- Memory T cell
- T cell
- Adoptive cell transfer
- Latent tuberculosis
- Population
- Tuberculosis
- IL-2 receptor
- C-C chemokine receptor type 7
- Mycobacterium tuberculosis
- Virology
- Immune system