Smad4 promotes differentiation of effector and circulating memory CD8 T cells but is dispensable for tissue-resident memory CD8 T cells

Yinghong Hu, Young Tae Lee, Susan M. Kaech, Beth Garvy, Linda S. Cauley

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

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.

Original languageEnglish
Pages (from-to)2407-2414
Number of pages8
JournalJournal of Immunology
Volume194
Issue number5
DOIs
StatePublished - Mar 1 2015

Bibliographical note

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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