ePoster Presentation 49th Annual Scientific Meeting of the Australian and New Zealand Society for Immunology 2021

Characterising the role of human Vδ2 T cells in Plasmodium falciparum specific antibody development (#241)

Nicholas Dooley 1 2 , Megan Soon 2 , Jessica Loughland 2 , Dean Andrew 2 , Damian Oyong 3 , Rebecca Webster 2 , Nicholas Anstey 3 , Bridget Barber 2 , Michelle Boyle 2
  1. Griffith University, Brisbane, Queensland, Australia
  2. QIMR Berghofer, Brisbane, Queensland, Australia
  3. Menzies School of Health Research, Darwin, Northern Territory

Repeat exposures to Plasmodium falciparum (Pf) does not rapidly induce the development of long-lived malaria immunity, and antibody responses induced by vaccines have short-lived protection. Vδ2 T cells are a subset of γδ T cells that act to enhance the inflammatory immune response to malaria. In addition to innate responsiveness, we propose that Vδ2 T cells contribute directly to malarial antibody development. We investigated the role of humanVδ2 T cells in antigen-presentation and B cell activation by utilising experimental and naturally-acquired malaria infection models. We co-cultured malaria-naive healthy peripheral blood mononuclear cells with blood-stage Pf, and observed increased Vδ2 T cell expression of both antigen-presenting cell (APC) surface antigens, HLA-DR, CD86 and CD40, and B cell activating surface antigens, CD40L and ICOS. In parasite co-cultures, malaria-naive Vδ2 T cells produced pro-inflammatory cytokines, IFNγ and TNF, but not cytokines previously implicated in malaria antibody induction, IL-4, IL-10 or IL-21. However, Vδ2 T cells from individuals with an acute, naturally-acquired malaria infection did produce antibody-inducing cytokines IL-10 and IL-21. We confirmed this phenotype in an Induced Blood-stage Malaria trial (IBSM), where we intravenously inoculated malaria-naive adults (n = 12) with blood-stage Pf. In this cohort, we observed increased Vδ2 T cell expression of surface antigens HLA-DR, CD86 and ICOS, at fifteen days post-inoculation. Data shows the induction of an APC/B cell activating Vδ2 T cell phenotype after malaria-naive Pf infection both in vitro and during an experimental IBSM model. Furthermore, we show the relevance of this phenotype in natural-acquired malaria, demonstrated by increased production of cytokines related to B cell activation during active infection. These results identify a novel and unconventional Vδ2 T cell phenotype activated during Pf infection.