Involvement of CD8⁺ T cells in protective immunity against murine blood‐stage infection with Plasmodium yoelii 17XL strain

Abstract

When developing malaria vaccines, the most crucial step is to elucidate the mechanisms involved in protective immunity against the parasites. We found that CD8+ T cells contribute to protective immunity against infection with blood‐stage parasites of Plasmodium yoelii. Infection of C57BL/6 mice with P. yoelii 17XL was lethal, while all mice infected with a low‐virulence strain of the parasite 17XNL acquired complete resistance against re‐infection with P. yoelii 17XL. However, the host mice transferred with CD8+ T cells from mice primed only with P. yoelii 17XNL failed to acquire protective immunity. On the other hand, the irradiated host mice were completely resistant to P. yoelii 17XL infection, showing no grade of parasitemia when adoptively transferred with CD8+ T cells from immune mice that survived infection with both P. yoelii XNL and, subsequently, P. yoelii 17XL. These protective CD8+ T cells from immune WT mice had the potential to generate IFN‐γ, perforin (PFN) and granzyme B. When mice deficient in IFN‐γ were used as donor mice for CD8+ T cells, protective immunity in the host mice was fully abrogated, and the immunity was profoundly attenuated in PFN‐deficient mice. Thus, CD8+ T cells producing IFN‐γ and PFN appear to be involved in protective immunity against infection with blood‐stage malaria.

IL‐23 protection against Plasmodium berghei infection in mice is partially dependent on IL‐17 from macrophages

“…However, a protective role for neutrophils in malaria is supposed to be less important [41]; therefore, the decrease in neutrophils is hard to explain on the basis of the impaired resistance of these mice to malaria. In contrast, macrophages are known to be important for protection against blood-stage malaria as they phagocytose and digest parasitized RBCs [27,28]. While there was increase or a slight loss of splenic macrophages in the WT mice after PbNK infection, splenic macrophages from mutant mice infected with PbNK were markedly reduced (Figs.…”

“…As shown in Figure 4A and B, a dramatic reduction in the number of CD11b + cells in p19KO mice occurred irrespective of IL-17 production. To investigate the possibility that macrophages (which are crucial for eradication of malaria parasites [27,28] via ingesting and digesting parasitized RBCs) are involved in IL-23-dependent protection, we conducted a detailed analysis of such cells. In the absence of infection, comparable numbers of macrophages within p19KO and 17KO mouse spleens were identified.…”

Immunophenotyping of blood mononuclear cells from P. berghei (NK-65) infected and immunized BALB/c mice

“…The consequences of increased number of CD4 ? cells in P. vivax infected people render a proinflammatory environment including induction of nitric oxide synthase, antimicrobial peptides and other cytokines leading to a favorable immune response against the parasite (Imai et al 2010). Lau et al (2011) reported 30 % splenic CD8 ?…”

“…IFN-c from CD8 ? T cells activates the macrophages leading to the phagocytosis of parasitized erythrocytes (Imai et al 2010). In present study also, TPA immunized mice showed significant increase in the frequencies of CD8 ?…”

An Essential Role for C5aR Signaling in the Optimal Induction of a Malaria-Specific CD4+ T Cell Response by a Whole-Killed Blood-Stage Vaccine

“…Consistent with this observation, we also found that activation of the malariaspecific CD8 + T cells was depressed in the absence of C5aR (data not shown). Although one report recently showed that CD8 + T cells were involved in protection against the blood stage of malaria (36), most studies excluded the protective effect of CD8 + T cells in mice either treated with drug or immunized with a whole blood-stage malaria vaccine (10,37). Therefore, we did not pursue investigation into the regulatory role of C5a with regard to the activation of malaria-specific CD8 + T cells.…”