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

Publication Type:

Journal Article

Authors:

Moguche, Albanus O; Shafiani, Shahin; Clemons, Corey; Larson, Ryan P; Dinh, Crystal; Higdon, Lauren E; Cambier, C J; Sissons, James R; Gallegos, Alena M; Fink, Pamela J; Urdahl, Kevin B

Source:

J Exp Med, Volume 212, Issue 5, p.715-28 (2015)

Keywords:

Animals, DNA-Binding Proteins, Gene Expression Regulation, Immunity, Cellular, Immunologic Memory, Inducible T-Cell Co-Stimulator Protein, Lung, Mice, Mice, Knockout, Mycobacterium tuberculosis, Proto-Oncogene Proteins c-bcl-6, Th1 Cells, Tuberculosis, Pulmonary

Abstract:

<p>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.</p>