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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.

SUBMITTER: Siegel AM 

PROVIDER: S-EPMC3228524 | biostudies-other | 2011 Nov

REPOSITORIES: biostudies-other

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

Siegel Andrea M AM   Heimall Jennifer J   Freeman Alexandra F AF   Hsu Amy P AP   Brittain Erica E   Brenchley Jason M JM   Douek Daniel C DC   Fahle Gary H GH   Cohen Jeffrey I JI   Holland Steven M SM   Milner Joshua D JD  

Immunity 20111101 5


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. Nai  ...[more]

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