In Brief

Immune Regulation

Malaria blood-stage suppression of liver-stage immunity by dendritic cells. Ocaña-Morgner, C. et al. J. Exp. Med. 197, 143–151 (2003)

Malaria infection is initiated when an infected mosquito injects sporozoites into a mammalian host. The sporozoites invade the liver, where development and replication lead to the production of merozoites, which can infect erythrocytes — the blood stage of the infection. Using a rodent malaria model, this study shows that the blood stage of the infection actively suppresses immune responses targeted at the liver stage of the disease. Irradiated sporozoites injected into mice induce a CD8⁺ T-cell response, whereas non-irradiated sporozites do not. When equal numbers of irradiated and non-irradiated sporozoites are injected, a CD8⁺ T-cell response does not develop, which indicates that the non-irradiated sporozoites are mediating a suppressive effect. This suppressive effect — inhibition of IFN-γ secretion by T cells — was found to be mediated by dendritic cells (DCs). Blood-stage parasites inhibit DC maturation, enhance IL-10 production and decrease IL-12 production, but the suppressive factor released by DCs has not been identified yet.

Regulatory Lymphocytes

Activation of human CD4⁺ cells with CD3 and CD46 induces a T-regulatory cell 1 phenotype. Kemper, C. et al. Nature 421, 388–392 (2003)

T regulatory 1 (T_R1) cells are a type of regulatory CD4⁺ T cell that produce IL-10 and can suppress the function of T helper cells, but the differentiation pathway of these cells remains unclear. Now, Claudia Kemper and colleagues show that complement regulatory protein — a transmembrane protein that inhibits complement activation on host cells — has a role in stimulating the development of T_R1 cells. Co-engagement of CD3 and CD46 in the presence of IL-2 induces a T_R1 phenotype of human CD4⁺ T cells. Supernatant from these T_R1-cell cultures suppresses the proliferation of bystander cells, a process that is inhibited by neutralizing IL-10-specific antibody.

Evolution

Urochordates and the origin of natural killer cells: identification of a CD94/NKR-P1-related receptor in blood cells of Botryllus. Khalturin, K. et al. Proc. Natl Acad. Sci. USA 100, 622–627 (2003)

Botryllus schlosseri is a colony-forming invertebrate chordate that can undergo transplantation reactions. When two colonies meet, they either fuse or develop a cytotoxic lesion at the point of contact. The authors screened for genes with levels of expression that were either up or downregulated after allorecognition between colonies. Of the 1,200 transcripts analysed, 50 were differentially regulated. One of these (BsCD94-1) was found to be a protein containing a C-type lectin domain, with homology to the natural killer (NK)-cell receptor CD94. CD94.1-expressing blood cells in Botryllus resemble granulocytes and might be ancestral NK cells.