Critical role for all-trans retinoic acid for optimal effector and effector memory CD8 T cell differentiation

S. Rameeza Allie, Weijun Zhang, Ching Yi Tsai, Randolph J. Noelle, Edward J. Usherwood

Research output: Contribution to journalArticlepeer-review

Abstract

A plethora of work implicates important effects of the vitamin A derivative retinoic acid (RA) in myeloid differentiation, whereas fewer studies explore the role of RA in lymphoid cells. Most work on lymphoid cells has focused on the influence of RA on CD4 T cells. Little information about the role of RA in CD8 T cell differentiation is available, and even less on cell-intrinsic effects in the CD8 T cell. This study explores the role of RA in effector and memory differentiation in a cell-intrinsic manner in the context of vaccinia virus infection. We observed the loss of the short-lived effector cell phenotype (reduced KLRG1+, T-bethi, granzyme Bhi), accompanied by an enhanced memory precursor phenotype at the effector (increased CD127hi, IL-2+) and contraction phases (increased CD127hi, IL-2+, eomesoderminhi) of the CD8 response in the absence of RA signaling. The lack of RA also increased the proportion of central memory CD8s. Collectively, these results introduce a new role for RA in CD8 T cell activation and differentiation. This new role may have significant implications for optimal vaccine design in which vitamin A supplementation is used to augment effector responses, but it may be to the detriment of the long-term central memory response.

Original languageEnglish (US)
Pages (from-to)2178-2187
Number of pages10
JournalJournal of Immunology
Volume190
Issue number5
DOIs
StatePublished - Mar 1 2013

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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