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PLoS One. 2011 May 12;6(5):e19864. doi: 10.1371/journal.pone.0019864.

T cells from Programmed Death-1 deficient mice respond poorly to Mycobacterium tuberculosis infection.

Author information

1
Immunology Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, India.

Abstract

BACKGROUND:

Programmed Death-1 (PD-1; CD279) receptor molecule is widely believed to be a negative regulator predominantly expressed by exhausted/activated mouse T cells. Upon interaction with its ligands, PD-L1 and PD-L2, PD-1 inhibits activation of T cells and cytokine production, which has been documented in various viral and fungal infections as well as in vitro studies. Therefore, inhibition of T cell responses by PD-1 resulted in disease resistance in a variety of mouse infection models studied heretofore.

METHODOLOGY/PRINCIPAL FINDINGS:

Here, we report that PD-1 deficient (PD-1(-/-)) mice infected with Mycobacterium tuberculosis (M. tb) H37Rv by the aerosol route have increased susceptibility as compared with their wild type littermates. Surprisingly, M. tb antigen-specific T cell proliferation was dramatically reduced in PD-1 deficient animals compared with wild-type littermates, and this was due to increased numbers of regulatory T cells (Tregs) and recruitment of mesenchymal stem cells. Furthermore, PD-1(-/-) mice exhibited decreases in the autophagy-induced LC3-B marker protein in macrophages.

CONCLUSIONS/SIGNIFICANCE:

Our findings suggest that PD-1 does not play an inhibitory role during M. tb infection and instead promotes mycobacterial clearance in mice.

PMID:
21589883
PMCID:
PMC3093409
DOI:
10.1371/journal.pone.0019864
[Indexed for MEDLINE]
Free PMC Article

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