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PMID: 22118528 Published · ppublish English Journal Article Research Support, N.I.H., Intramural

A critical role for STAT3 transcription factor signaling in the development and maintenance of human T cell memory.

Immunity ·Vol. 35 ·No. 5 ·2011-11-23 ·Pages 806-18

Siegel AM, Heimall J, Freeman AF, Hsu AP, Brittain E, Brenchley JM, Douek DC, Fahle GH, Cohen JI, Holland SM, Milner JD

Abstract

STAT3 transcription factor signaling in specific T helper cell differentiation has been well described, although the broader roles for STAT3 in lymphocyte memory are less clear. Patients with autosomal-dominant hyper-IgE syndrome (AD-HIES) carry dominant-negative STAT3 mutations and are susceptible to a variety of bacterial and fungal infections. We found that AD-HIES patients have a cell-intrinsic defect in the number of central memory CD4(+) and CD8(+) T cells compared to healthy controls. Naive T cells from AD-HIES patients had lower expression of memory-related transcription factors BCL6 and SOCS3, a primary proliferation defect, and they failed to acquire central memory-like surface phenotypes in vitro. AD-HIES patients showed a decreased ability to control varicella zoster virus (VZV) and Epstein-Barr virus (EBV) latency, and T cell memory to both of these viruses was compromised. These data point to a specific role for STAT3 in human central memory T cell formation and in control of certain chronic viruses.

MeSH Terms
Adolescent Adult Apoptosis/genetics,immunology Base Sequence Child Child, Preschool Epstein-Barr Virus Infections/immunology Female Gene Expression Regulation, Developmental Herpesvirus 3, Human/immunology Humans Immunologic Memory/genetics Job Syndrome/genetics,immunology,virology Male Middle Aged Mutation Phenotype STAT3 Transcription Factor/genetics,metabolism Signal Transduction T-Lymphocytes/immunology,metabolism Young Adult
Chemicals
STAT3 Transcription Factor
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Siegel Andrea M
Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Heimall Jennifer
Freeman Alexandra F
Hsu Amy P
Brittain Erica
Brenchley Jason M
Douek Daniel C
Fahle Gary H
Cohen Jeffrey I
Holland Steven M
Milner Joshua D
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Article Info
Journal
Immunity
Abbr.
Immunity
ISSN
1097-4180
DOI
10.1016/j.immuni.2011.09.016
Published
2011-11-23
Pages
806-18
Language
English
Region
United States
NLM ID
9432918
PMCID
PMC3228524
Subset
IM
Grants
Intramural NIH HHS · ZIA AI001098-03 · United States
Corrections
CommentIn
PMID: 22118521
External Links
PubMed source DOI: 10.1016/j.immuni.2011.09.016 PMC Full Text View journal details
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