期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 115, 期 41, 页码 10416-10421出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1808339115
关键词
Salmonella infection; CD4 T cell; protective immunity; tissue-resident memory; vaccines
资金
- NIH T32 training Grant [AI060555]
- National Institute of Allergy and Infectious Diseases [AI056172, AI103422, AI139410]
- National Health and Medical Research Council (NHMRC) Program [1092262]
- NHMRC [1059937]
- National Health and Medical Research Council of Australia [1059937] Funding Source: NHMRC
While CD4 Th1 cells are required for resistance to intramacrophage infections, adoptive transfer of Th1 cells is insufficient to protect against Salmonella infection. Using an epitope-tagged vaccine strain of Salmonella, we found that effective protection correlated with expanded Salmonella-specific memory CD4 T cells in circulation and nonlymphoid tissues. However, naive mice that previously shared a blood supply with vaccinated partners lacked T cell memory with characteristics of tissue residence and did not acquire robust protective immunity. Using a YFP-IFN-gamma. reporter system, we identified Th1 cells in the liver of immunized mice that displayed markers of tissue residence, including P2X7, ARTC2, LFA-1, and CD101. Adoptive transfer of liver memory cells after ARTC2 blockade increased protection against highly virulent bacteria. Taken together, these data demonstrate that noncirculating memory Th1 cells are a vital component of immunity to Salmonella infection and should be the focus of vaccine strategies.
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