Title

Smad4 Promotes Differentiation of Effector and Circulating Memory CD8 T Cells but Is Dispensable for Tissue-Resident Memory CD8 T Cells

Abstract

Tissue-resident memory CD8 T cells are a unique subset of virus-specific CTLs that bolster local immune responses after becoming lodged in previously infected tissues. These cells provide enhanced protection by intercepting returning pathogens before a new infection gets established. In contrast, central memory CD8 T cells circulate in the bloodstream and proliferate in secondary lymphoid organs before replenishing effector and memory CD8 T cell populations in remote parts of the body. Both populations of virus-specific memory CD8 T cells participate in immunity to influenza virus infection; however, the signaling pathways that instruct developing memory CD8 T cells to distribute to specific tissues are poorly defined. We show that TGF-β promotes the development of pulmonary tissue-resident memory T cells via a signaling pathway that does not require the downstream signaling intermediate Sma- and Mad-related protein (Smad)4. In contrast, circulating memory CD8 T cells have no requirement for TGF-β but show signs of arrested development in the absence of Smad4, including aberrant CD103 expression. These signaling pathways alter the distribution of virus-specific CTLs in the lungs but do not prevent robust cytokine responses. Our data show that Smad4 is required for normal differentiation of multiple subsets of virus-specific CD8 T cells. In normal circumstances, Smad4 may be activated via a pathway that bypasses the TGF-β receptor. Improved understanding of these signaling pathways could be used to augment vaccine-induced immunity.

Document Type

Article

Publication Date

3-1-2015

Notes/Citation Information

Published in The Journal of Immunology, v. 194, no. 5, p. 2407-2414.

Copyright © 2015 by The American Association of Immunologists, Inc.

Digital Object Identifier (DOI)

https://doi.org/10.4049/jimmunol.1402369

Funding Information

This work was supported by National Institutes of Health Grant AI056172.

Related Content

The online version of this article contains supplemental material.

Share

COinS