Pathogen-Specific Treg Cells Expand Early during Mycobacterium tuberculosis Infection but Are Later Eliminated in Response to Interleukin-12

Shahin Shafiani, Crystal Dinh, JamesM Ertelt, AlbanusO Moguche, Imran Siddiqui, KateS Smigiel, Pawan Sharma, DanielJ Campbell, SingSing Way, KevinB Urdahl

Research output: Contribution to journalArticle

Abstract

Thymically derived Foxp3+ regulatory T (Treg) cells have a propensity to recognize self-peptide:MHC complexes, but their ability to respond to epitope-defined foreign antigens during infectious challenge has not been demonstrated. Here we show that pulmonary infection with Mycobacterium tuberculosis (Mtb), but not Listeria monocytogenes (Lm), induced robust lymph node expansion of a highly activated population of pathogen-specific Treg cells from the pre-existing pool of thymically derived Treg cells. These antigen-specific Treg cells peaked in numbers 3weeks after infection but subsequently underwent selective elimination driven, in part, by interleukin-12-induced intrinsic expression of the Th1-cell-promoting transcription factor T-bet. Thus, the initial Mtb-induced inflammatory response promotes pathogen-specific Treg cell proliferation, but these cells are actively culled later, probably to prevent suppression during later stages of infection. These findings have important implications for the prevention and treatment of tuberculosis and other chronic diseases in which antigen-specific Treg cells restrict immunity.

Original languageEnglish
Pages (from-to)1261-1270
Number of pages10
JournalImmunity
Volume38
Issue number6
DOIs
Publication statusPublished - Jun 27 2013

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Immunology

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    Shafiani, S., Dinh, C., Ertelt, J., Moguche, A., Siddiqui, I., Smigiel, K., Sharma, P., Campbell, D., Way, S., & Urdahl, K. (2013). Pathogen-Specific Treg Cells Expand Early during Mycobacterium tuberculosis Infection but Are Later Eliminated in Response to Interleukin-12. Immunity, 38(6), 1261-1270. https://doi.org/10.1016/j.immuni.2013.06.003