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J Exp Med. 2015 May 4;212(5):715-28. doi: 10.1084/jem.20141518. Epub 2015 Apr 27.

ICOS and Bcl6-dependent pathways maintain a CD4 T cell population with memory-like properties during tuberculosis.

Author information

1
Seattle Biomedical Research Institute (renamed Center for Infectious Disease Research), Seattle, WA 98109 Department of Immunology, University of Washington School of Medicine, Seattle, WA 98104.
2
Seattle Biomedical Research Institute (renamed Center for Infectious Disease Research), Seattle, WA 98109.
3
Department of Immunology, University of Washington School of Medicine, Seattle, WA 98104.
4
Department of Immunology, International Centre for Genetic Engineering and Biotechnology, New Delhi 110067, India.
5
Seattle Biomedical Research Institute (renamed Center for Infectious Disease Research), Seattle, WA 98109 Department of Immunology, University of Washington School of Medicine, Seattle, WA 98104 kevin.urdahl@cidresearch.org.

Abstract

Immune control of persistent infection with Mycobacterium tuberculosis (Mtb) requires a sustained pathogen-specific CD4 T cell response; however, the molecular pathways governing the generation and maintenance of Mtb protective CD4 T cells are poorly understood. Using MHCII tetramers, we show that Mtb-specific CD4 T cells are subject to ongoing antigenic stimulation. Despite this chronic stimulation, a subset of PD-1(+) cells is maintained within the lung parenchyma during tuberculosis (TB). When transferred into uninfected animals, these cells persist, mount a robust recall response, and provide superior protection to Mtb rechallenge when compared to terminally differentiated Th1 cells that reside preferentially in the lung-associated vasculature. The PD-1(+) cells share features with memory CD4 T cells in that their generation and maintenance requires intrinsic Bcl6 and intrinsic ICOS expression. Thus, the molecular pathways required to maintain Mtb-specific CD4 T cells during ongoing infection are similar to those that maintain memory CD4 T cells in scenarios of antigen deprivation. These results suggest that vaccination strategies targeting the ICOS and Bcl6 pathways in CD4 T cells may provide new avenues to prevent TB.

PMID:
25918344
PMCID:
PMC4419347
DOI:
10.1084/jem.20141518
[Indexed for MEDLINE]
Free PMC Article

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