A Critical Role for STAT3 Transcription Factor Signaling in the Development and Maintenance of Human T Cell Memory

SummarySTAT3 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.

Graphical AbstractFigure optionsDownload full-size imageDownload high-quality image (217 K)Download as PowerPoint slideHighlights► Patients with AD-HIES have reduced number of central memory CD4 and CD8 T cells ► The reduction of central memory T cell numbers is T cell intrinsic ► Naive T cells from patients express decreased memory-related transcription factors ► HIES patients have an increased incidence of shingles and EBV viremia