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The adaptor molecule CD2AP in CD4 T cells modulates differentiation of follicular helper T cells during chronic LCMV infection.

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  • معلومة اضافية
    • Author-Supplied Keywords:
      Animal cells
      Antibodies
      Antibody-producing cells
      B cells
      Biochemistry
      Biology and life sciences
      Blood cells
      Cell biology
      Cell differentiation
      Cell signaling
      Cellular types
      Cytotoxic T cells
      Developmental biology
      Immune cells
      Immune physiology
      Immune response
      Immune system proteins
      Immunology
      Medicine and health sciences
      Physiology
      Proteins
      Research Article
      Signal transduction
      Signaling cascades
      T cells
      TCR signaling cascade
      White blood cells
    • NAICS/Industry Codes:
      112990 All Other Animal Production
    • Abstract:
      CD4 T cell-mediated help to CD8 T cells and B cells is a critical arm of the adaptive immune system required for control of pathogen infection. CD4 T cells express cytokines and co-stimulatory molecules that support a sustained CD8 T cell response and also enhance generation of protective antibody by germinal center B cells. However, the molecular components that modulate CD4 T cell functions in response to viral infection or vaccine is incompletely understood. Here we demonstrate that inactivation of the signaling adaptor CD2-associated protein (CD2AP) promotes CD4 T cell differentiation towards the follicular helper lineage, leading to enhanced control of viral infection by augmented germinal center response in chronic lymphocytic choriomeningitis virus (LCMV) infection. The enhanced follicular helper differentiation is associated with extended duration of TCR signaling and enhanced cytokine production of CD2AP-deficient CD4 T cells specifically under TH1 conditions, while neither prolonged TCR signaling nor enhanced follicular helper differentiation was observed under conditions that induce other helper effector subsets. Despite the structural similarity between CD2AP and the closely related adaptor protein CIN85, we observed defective antibody-mediated control of chronic LCMV infection in mice lacking CIN85 in T cells, suggesting non-overlapping and potentially antagonistic roles for CD2AP and CIN85. These results suggest that tuning of TCR signaling by targeting CD2AP improves protective antibody responses in viral infection. [ABSTRACT FROM AUTHOR]
    • Abstract:
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    • Author Affiliations:
      1Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, Missouri, United States of America
      2Laboratory for Lymphocyte Differentiation, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan
      3Laboratory of Lymphocyte Differentiation, WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan
    • Full Text Word Count:
      10333
    • ISSN:
      1553-7366
    • Accession Number:
      10.1371/journal.ppat.1007053
    • Accession Number:
      129480399
  • Citations
    • ABNT:
      RAJU, S. et al. The adaptor molecule CD2AP in CD4 T cells modulates differentiation of follicular helper T cells during chronic LCMV infection. PLoS Pathogens, [s. l.], v. 14, n. 5, p. 1–20, 2018. DOI 10.1371/journal.ppat.1007053. Disponível em: http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=asn&AN=129480399&custid=s8280428. Acesso em: 15 ago. 2020.
    • AMA:
      Raju S, Kometani K, Kurosaki T, Shaw AS, Egawa T. The adaptor molecule CD2AP in CD4 T cells modulates differentiation of follicular helper T cells during chronic LCMV infection. PLoS Pathogens. 2018;14(5):1-20. doi:10.1371/journal.ppat.1007053
    • APA:
      Raju, S., Kometani, K., Kurosaki, T., Shaw, A. S., & Egawa, T. (2018). The adaptor molecule CD2AP in CD4 T cells modulates differentiation of follicular helper T cells during chronic LCMV infection. PLoS Pathogens, 14(5), 1–20. https://doi.org/10.1371/journal.ppat.1007053
    • Chicago/Turabian: Author-Date:
      Raju, Saravanan, Kohei Kometani, Tomohiro Kurosaki, Andrey S. Shaw, and Takeshi Egawa. 2018. “The Adaptor Molecule CD2AP in CD4 T Cells Modulates Differentiation of Follicular Helper T Cells during Chronic LCMV Infection.” PLoS Pathogens 14 (5): 1–20. doi:10.1371/journal.ppat.1007053.
    • Harvard:
      Raju, S. et al. (2018) ‘The adaptor molecule CD2AP in CD4 T cells modulates differentiation of follicular helper T cells during chronic LCMV infection’, PLoS Pathogens, 14(5), pp. 1–20. doi: 10.1371/journal.ppat.1007053.
    • Harvard: Australian:
      Raju, S, Kometani, K, Kurosaki, T, Shaw, AS & Egawa, T 2018, ‘The adaptor molecule CD2AP in CD4 T cells modulates differentiation of follicular helper T cells during chronic LCMV infection’, PLoS Pathogens, vol. 14, no. 5, pp. 1–20, viewed 15 August 2020, .
    • MLA:
      Raju, Saravanan, et al. “The Adaptor Molecule CD2AP in CD4 T Cells Modulates Differentiation of Follicular Helper T Cells during Chronic LCMV Infection.” PLoS Pathogens, vol. 14, no. 5, May 2018, pp. 1–20. EBSCOhost, doi:10.1371/journal.ppat.1007053.
    • Chicago/Turabian: Humanities:
      Raju, Saravanan, Kohei Kometani, Tomohiro Kurosaki, Andrey S. Shaw, and Takeshi Egawa. “The Adaptor Molecule CD2AP in CD4 T Cells Modulates Differentiation of Follicular Helper T Cells during Chronic LCMV Infection.” PLoS Pathogens 14, no. 5 (May 7, 2018): 1–20. doi:10.1371/journal.ppat.1007053.
    • Vancouver/ICMJE:
      Raju S, Kometani K, Kurosaki T, Shaw AS, Egawa T. The adaptor molecule CD2AP in CD4 T cells modulates differentiation of follicular helper T cells during chronic LCMV infection. PLoS Pathogens [Internet]. 2018 May 7 [cited 2020 Aug 15];14(5):1–20. Available from: http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=asn&AN=129480399&custid=s8280428