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Development of a Novel CD4+ TCR Transgenic Line That Reveals a Dominant Role for CD8+ Dendritic Cells and CD40 Signaling in the Generation of Helper and CTL Responses to Blood-Stage Malaria.

  • Fernandez-Ruiz, Daniel1, 2
  • Lau, Lei Shong1
  • Ghazanfari, Nazanin1, 2
  • Jones, Claerwen M1
  • Ng, Wei Yi1
  • Davey, Gayle M1
  • Berthold, Dorothee1
  • Holz, Lauren1, 2
  • Kato, Yu1
  • Enders, Matthias H1
  • Bayarsaikhan, Ganchimeg1, 3
  • Hendriks, Sanne H1
  • Lansink, Lianne I M4
  • Engel, Jessica A4
  • Soon, Megan S F4
  • James, Kylie R4
  • Cozijnsen, Anton5
  • Mollard, Vanessa5
  • Uboldi, Alessandro D6
  • Tonkin, Christopher J6
  • And 8 more
Published Article
The Journal of Immunology
The American Association of Immunologists
Publication Date
Dec 15, 2017
DOI: 10.4049/jimmunol.1700186
PMID: 29084838


We describe an MHC class II (I-Ab)-restricted TCR transgenic mouse line that produces CD4+ T cells specific for Plasmodium species. This line, termed PbT-II, was derived from a CD4+ T cell hybridoma generated to blood-stage Plasmodium berghei ANKA (PbA). PbT-II cells responded to all Plasmodium species and stages tested so far, including rodent (PbA, P. berghei NK65, Plasmodium chabaudi AS, and Plasmodium yoelii 17XNL) and human (Plasmodium falciparum) blood-stage parasites as well as irradiated PbA sporozoites. PbT-II cells can provide help for generation of Ab to P. chabaudi infection and can control this otherwise lethal infection in CD40L-deficient mice. PbT-II cells can also provide help for development of CD8+ T cell-mediated experimental cerebral malaria (ECM) during PbA infection. Using PbT-II CD4+ T cells and the previously described PbT-I CD8+ T cells, we determined the dendritic cell (DC) subsets responsible for immunity to PbA blood-stage infection. CD8+ DC (a subset of XCR1+ DC) were the major APC responsible for activation of both T cell subsets, although other DC also contributed to CD4+ T cell responses. Depletion of CD8+ DC at the beginning of infection prevented ECM development and impaired both Th1 and follicular Th cell responses; in contrast, late depletion did not affect ECM. This study describes a novel and versatile tool for examining CD4+ T cell immunity during malaria and provides evidence that CD4+ T cell help, acting via CD40L signaling, can promote immunity or pathology to blood-stage malaria largely through Ag presentation by CD8+ DC.

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