12 research outputs found
SUPERSIZED ESR – Strategien für eine weitere Vergrößerung und Optimierung des ESU Prozesses
Atypical idiopathic inflammatory demyelinating lesions (IIDL) : conventional and diffusion-weighted MR imaging (DWI) findings in 42 cases
Hypericin- and mTHPC-mediated photodynamic therapy for the treatment of cariogenic bacteria
Intrapulmonary shunt after cardiopulmonary bypass: The use of vital capacity maneuvers versus off-pump coronary artery bypass grafting
Interleukin-12 and B7.1 co-stimulation cooperate in the induction of effective antitumor immunity and therapy of established tumors
The Effects of Swiprosin-1 on the Formation of Pseudopodia-Like Structures and β-Adrenoceptor Coupling in Cultured Adult Rat Ventricular Cardiomyocytes
Functional STAT3 deficiency compromises the generation of human T follicular helper cells
T follicular helper (Tfh) cells are critical for providing the necessary signals to induce differentiation of B cells into memory and Ab-secreting cells. Accordingly, it is important to identify the molecular requirements for Tfh cell development and function. We previously found that IL-12 mediates the differentiation of human CD4 + T cells to the Tfh lineage, because IL-12 induces naive human CD4 + T cells to acquire expression of IL-21, BCL6, ICOS, and CXCR5, which typify Tfh cells. We have now examined CD4 + T cells from patients deficient in IL-12Rp1, TYK2, STAT1, and STAT3 to further explore the pathways involved in human Tfh cell differentiation. Although STAT1 was dispensable, mutations in IL12RB1, TYK2, or STAT3 compromised IL-12-induced expression of IL-21 by human CD4 + T cells. Defective expression of IL-21 by STAT3-deficient CD4 + T cells resulted in diminished B-cell helper activity in vitro. Importantly, mutations in STAT3, but not IL12RB1 or TYK2, also reduced Tfh cell generation in vivo, evidenced by decreased circulating CD4 +CXCR5 + T cells. These results highlight the nonredundant role of STAT3 in human Tfh cell differentiation and suggest that defective Tfh cell development and/or function contributes to the humoral defects observed in STAT3-deficient patients