Blimp-1 promotes terminal differentiation of virus-specific CD8 T cells and represses the acquisition of central memory T cell properties

By R. Rutishauser, G. Martins, S. Kalachikov, A. Chandele, I. Parish, E. Meffre, Joshy Jacob, K. Calame, S. Kaech. Immunity, 2009

629 citations recorded by the source corpus.

SUMMARY During acute infections, a small population of effector CD8 T cells evades terminal differentiation and survives as long-lived memory T cells. We demonstrate that the transcriptional repressor Blimp-1 enhances the formation of terminally differentiated CD8 T cells during LCMV infection, and Blimp-1 deficiency promotes the acquisition of memory cell properties by effector cells. Blimp-1 expression is preferentially increased in terminally differentiated effector and “effector memory” (TEM) CD8 T cells, and gradually decays after infection as central memory (TCM) cells develop. Blimp-1-/- effector CD8 T cells show some reduction in effector molecule expression, but primarily develop into memory precursor cells that survive better, and more rapidly acquire several TCM attributes, including CD62L and IL-2 expression and enhanced proliferative responses. These results reveal a critical role for Blimp-1 in controlling terminal differentiation and suppressing memory cell developmental potential in effector CD8 T cells during viral infection.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/21cde4149ae750bace254c4934e0fb5a3fb8ff5f

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1. M. Bevan
2. V. Badovinac
3. J. Harty
4. Shane Crotty
5. Rafi Ahmed
6. T. Malek
7. I. Castro
8. W. Nicholas Haining

Citations in the corpus

• The transcription factors Blimp-1 and IRF4 jointly control the differentiation and function of effector regulatory T cells (2011, background): “In mouse models of virus infection, Blimp-1 is required for the differentiation of CD8 + cytotoxic effector T cells and functional memory cell”
• Interleukin-2 and Inflammation Induce Distinct Transcriptional Programs that Promote the Differentiation of Effector Cytolytic T Cells (2010, background): “Studies of gene-disrupted mice have shown that Blimp-1 and Bcl6 are required in vivo for the development of effector and memory CTL, respectively (Ichii et al., 2002; Rutishauser et al., 2009).”
• Interleukin-2 Receptor Signaling: At the Interface between Tolerance and Immunity (2010, positive): “This step depends upon the transcriptional repressor Blimp-1, which promotes the SLEC and TE fate and directly represses IL-2 transcription (Kallies et al., 2009; Rutishauser et al., 2009).”
• Bcl6 dependent T follicular helper cell differentiation diverges from effector cell differentiation during priming and depends on the gene Icos (2011, positive): “Immunity 34, 932–946, June 24, 2011 ª2011 Elsevier Inc. 943 require Blimp1 for their full functionality (Kallies et al., 2009; Rutishauser et al., 2009).”
• CD8+ T Cells: Foot Soldiers of the Immune System (2011, neutral): “However, a migratory defect is not obvious during LCMV infection (Rutishauser et al., 2009).”
• Differentiation and persistence of memory CD8+ T cells depend on T cell factor 1 (2010, background): “In line with this notion, TCF-1 expression was upregulated approximately 10-fold in Blimp-1-deficient CD8+ effector cells (Rutishauser et al., 2009).”
• Prolonged interleukin-2Ralpha expression on virus-specific CD8+ T cells favors terminal-effector differentiation in vivo. (2010, background): “previous reports that Blimp-1 expression is upregulated by increased IL-2 signals (Calame, 2008; Gong and Malek, 2007; Malek, 2008), and that Blimp-1 drives terminal-effector differentiation ( Rutishauser et al., 2009 ), CD25hi cells that are capable”