CD1-restricted adaptive immune responses to Mycobacteria in human group 1 CD1 transgenic mice

Kyrie Felio, Hanh Nguyen, Christopher C. Dascher, Hak Jong Choi, Sha Li, Michael I. Zimmer, Angela Colmone, D. Branch Moody, Michael B. Brenner, Chyung Ru Wang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

79 Scopus citations

Abstract

Group 1 CD1 (CD1a, CD1b, and CD1c)-restricted T cells recognize mycobacterial lipid antigens and are found at higher frequencies in Mycobacterium tuberculosis (Mtb)-infected individuals. However, their role and dynamics during infection remain unknown because of the lack of a suitable small animal model. We have generated human group 1 CD1 transgenic (hCD1Tg) mice that express all three human group 1 CD1 isoforms and support the development of group 1 CD1-restricted T cells with diverse T cell receptor usage. Both mycobacterial infection and immunization with Mtb lipids elicit group 1 CD1-restricted Mtb lipid-specific T cell responses in hCD1Tg mice. In contrast to CD1d-restricted NKT cells, which rapidly respond to initial stimulation but exhibit anergy upon reexposure, group 1 CD1-restricted T cells exhibit delayed primary responses and more rapid secondary responses, similar to conventional T cells. Collectively, our data demonstrate that group 1 CD1-restricted T cells participate in adaptive immune responses upon mycobacterial infection and could serve as targets for the development of novel Mtb vaccines.

Original languageEnglish (US)
Pages (from-to)2497-2509
Number of pages13
JournalJournal of Experimental Medicine
Volume206
Issue number11
DOIs
StatePublished - Oct 26 2009

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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