Ex vivo lymphocyte phenotyping during Plasmodium falciparum sporozoite immunization in humans

EM Bijker, R Schats, LG Visser… - Parasite …, 2015 - Wiley Online Library
EM Bijker, R Schats, LG Visser, RW Sauerwein, A Scholzen
Parasite immunology, 2015Wiley Online Library
Immunization of malaria‐naïve volunteers under chemoprophylaxis with Plasmodium
falciparum sporozoites (CPS) efficiently and reproducibly induces sterile protection and thus
constitutes an excellent model to study protective immune responses against malaria. Here,
we performed the first longitudinal assessment of lymphocyte activation and differentiation
kinetics during sporozoite immunization in 15 volunteers by ex vivo lymphocyte flow
cytometry analysis. Both CD 4 and CD 8 T cells as well as γδT cells, NK cells and CD 3+ CD …
Summary
Immunization of malaria‐naïve volunteers under chemoprophylaxis with Plasmodium falciparum sporozoites (CPS) efficiently and reproducibly induces sterile protection and thus constitutes an excellent model to study protective immune responses against malaria. Here, we performed the first longitudinal assessment of lymphocyte activation and differentiation kinetics during sporozoite immunization in 15 volunteers by ex vivo lymphocyte flow cytometry analysis. Both CD4 and CD8 T cells as well as γδT cells, NK cells and CD3+ CD56+ cells showed increased activation and proliferation following immunization. Transient induction of the transcription factor T‐bet and the cytotoxic molecule granzyme B indicated a role of Th1 responses and cytotoxic T cells in CPS‐induced immunity. The absolute number of γδT cells as well as the proportion of granzyme B‐containing γδT cells showed a significant and sustained increase. Regulatory T‐cell (Treg) proliferation was significantly higher after the second immunization in subjects subsequently not protected against challenge infection. These findings indicate an important role for γδT cells, Th1 and cytotoxic responses in whole sporozoite immunization with a possibly suppressive role of Tregs.
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