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The transforming growth factor beta signaling pathway is critical for the formation of CD4 T follicular helper cells and isotype-switched antibody responses in the lung mucosa.
Marshall, Heather D; Ray, John P; Laidlaw, Brian J; Zhang, Nianzhi; Gawande, Dipika; Staron, Matthew M; Craft, Joe; Kaech, Susan M.
Afiliação
  • Marshall HD; Department of Immunobiology, Yale University School of Medicine, New Haven, United States.
  • Ray JP; Department of Immunobiology, Yale University School of Medicine, New Haven, United States.
  • Laidlaw BJ; Department of Immunobiology, Yale University School of Medicine, New Haven, United States.
  • Zhang N; Department of Immunobiology, Yale University School of Medicine, New Haven, United States.
  • Gawande D; Department of Immunobiology, Yale University School of Medicine, New Haven, United States.
  • Staron MM; Department of Immunobiology, Yale University School of Medicine, New Haven, United States.
  • Craft J; Department of Immunobiology, Yale University School of Medicine, New Haven, United States.
  • Kaech SM; Department of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, United States.
Elife ; 4: e04851, 2015 Jan 08.
Article em En | MEDLINE | ID: mdl-25569154
ABSTRACT
T follicular helper cells (Tfh) are crucial for the initiation and maintenance of germinal center (GC) reactions and high affinity, isotype-switched antibody responses. In this study, we demonstrate that direct TGF-ß signaling to CD4 T cells is important for the formation of influenza-specific Tfh cells, GC reactions, and development of isotype-switched, flu-specific antibody responses. Early during infection, TGF-ß signaling suppressed the expression of the high affinity IL-2 receptor α chain (CD25) on virus-specific CD4 T cells, which tempered IL-2 signaling and STAT5 and mammalian target of rapamycin (mTOR) activation in Tfh precursor CD4 T cells. Inhibition of mTOR allowed for the differentiation of Tfh cells in the absence of TGF-ßR signaling, suggesting that TGF-ß insulates Tfh progenitor cells from IL-2-delivered mTOR signals, thereby promoting Tfh differentiation during acute viral infection. These findings identify a new pathway critical for the generation of Tfh cells and humoral responses during respiratory viral infections.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transdução de Sinais / Fator de Crescimento Transformador beta / Linfócitos T Auxiliares-Indutores / Switching de Imunoglobulina / Pulmão / Formação de Anticorpos / Mucosa Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2015 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transdução de Sinais / Fator de Crescimento Transformador beta / Linfócitos T Auxiliares-Indutores / Switching de Imunoglobulina / Pulmão / Formação de Anticorpos / Mucosa Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2015 Tipo de documento: Article