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

K Felio, H Nguyen, CC Dascher, HJ Choi, S Li… - Journal of Experimental …, 2009 - rupress.org
K Felio, H Nguyen, CC Dascher, HJ Choi, S Li, MI Zimmer, A Colmone, DB Moody…
Journal of Experimental Medicine, 2009rupress.org
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 …
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.
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