Phenotypic and functional profiling of malaria-induced CD8 and CD4 T cells during blood-stage infection with Plasmodium yoelii

Joint ICGEB-Emory Vaccine Center, Aruna Asaf Ali Marg, New Delhi, India.
Immunology (Impact Factor: 3.8). 10/2010; 132(2):273-86. DOI: 10.1111/j.1365-2567.2010.03363.x
Source: PubMed


It is widely accepted that antibodies and CD4 T cells play critical roles in the immune response during the blood stage of malaria, whereas the role of CD8 T cells remains controversial. Here, we show that both CD8 and CD4 T cells robustly responded to an acute self-limiting blood-stage infection with Plasmodium yoelii. Similar to antigen-specific T cells, both CD8 and CD4 T cells showed dynamic expression of the surface proteins interleukin (IL)-7R and programmed death-1 (PD-1). Additionally, activated CD8 T cells showed differences in the expression of Killer cell lectin-like receptor G1, L-selectin and B cell lymphoma-2 and produced granzyme B, indicating cytotoxic activity, and the initially high expression of T-box transcription factor TBX21 in malaria-activated CD4 T cells indicated an early T helper type 1 (Th1)-skewed immune response. Our data demonstrate that blood-stage malaria infection results in a striking T-cell response and that activated CD8 and CD4 T cells have phenotypic and functional characteristics that are consistent with conventional antigen-specific effector and memory T cells. Therefore, a better understanding of the CD8 and CD4 T-cell response induced by blood-stage infection may prove to be essential in the development of a vaccine that targets the erythrocytic stage of the malarial parasite.

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    • "One of the first studies to examine PD-1 expression during malaria used a mouse model to show PD-1 expression on IL-7Rlo-expressing CD4+ and CD8+ T cells (Chandele et al., 2011). These PD-1-expressing cells (especially CD8+ T cells) were almost completely lost within 30 days of infection (Chandele et al., 2011). The study did not however measure functional responses to identify T cell exhaustion. "
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