title: A critical role for STAT3 transcription factor signaling in the development and maintenance of human T cell memory.
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.
authors: Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors: Andrea M
authors: AM
authors: Siegel
authors: Jennifer
authors: J
authors: Heimall
authors: Alexandra F
authors: AF
authors: Freeman
authors: Amy P
authors: AP
authors: Hsu
authors: Erica
authors: E
authors: Brittain
authors: Jason M
authors: JM
authors: Brenchley
authors: Daniel C
authors: DC
authors: Douek
authors: Gary H
authors: GH
authors: Fahle
authors: Jeffrey I
authors: JI
authors: Cohen
authors: Steven M
authors: SM
authors: Holland
authors: Joshua D
authors: JD
authors: Milner
mesh_terms: D000293:Adolescent; D000328:Adult; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D020031:Epstein-Barr Virus Infections / Q000276:immunology; D005260:Female; D018507:Gene Expression Regulation, Developmental; D014645:Herpesvirus 3, Human / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory / Q000235:genetics*; D007589:Job Syndrome / Q000235:genetics / Q000276:immunology / Q000821:virology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D050796:STAT3 Transcription Factor / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D055815:Young Adult
chemical_list: D050796:STAT3 Transcription Factor