Regulation of the CD8⁺ T cell responses against Plasmodium liver stages in mice

CD8⁺ T cells induced by immunization with Plasmodium sporozoites play a major role in protective immunity against parasite infection, inhibiting the development of liver stages. The activation of these T cells is initiated just a few hours after exposure to parasites and progresses rapidly through a tightly regulated program. Effector functions in CD8⁺ T are detectable as early as 24 h after immunization and this event is followed 24-48 h later by an accelerated expansion of the CD8⁺ T cell numbers which reaches a peak 4-5 days after priming. Concomitantly with the development of anti-parasite activity, CD8⁺ T cells acquire a self-regulatory role limiting the magnitude of the CD8⁺ T cell response. Once activated, CD8⁺ T cells strongly inhibit the priming of additional naive CD8⁺ T cells by competing for antigen presenting cells. On days 6-8 after immunization, a sudden contraction of this T cell response occurs due to programmed cell death of 70-80% of the activated cells. After this contraction phase, 15-20 days after priming, activated cells establish memory populations. The development and maintenance of these memory populations strictly depends on the presence of CD4⁺ T cells and IL-4, and probably also IL-7, IL-15 and IL-2. These cytokines, some of which are produced by CD4⁺ T cells, provide signals to prevents apoptosis and also induce the differentiation of memory sub-populations, most of which acquire definitive phenotypes 20-30 days after immunization.