学位論文 Expression of PD-1/LAG-3 and cytokine production by CD4+T cells during infection with Plasmodiumparasites

Doe, Henrietta Terko

60 ( 2 )  , pp.121 - 131 , 2016-03-18 , John Wiley & Sons Australia, Ltd
ISSN:03855600
内容記述
CD4+ T cells play critical roles in protection against the blood-stage of malaria infection, but their uncontrolled activation can be harmful to the host. We compared the expression of inhibitory receptors on activated CD4+ T cells and their cytokine production using rodent models of Plasmodium parasites, and compared them with those from a bacterial and another protozoan infection. CD4+ T cells from mice infected with P. yoelii 17XL, P yoelii 17XNL, P. chabaudi, P. vinckei, and P. berghei expressed the inhibitory receptors, PD-1 and LAG-3 as early as 6 days after infection, while those from either Listeria monocytogenes or Leishmania major-infected mice did not. In response to T-cell receptor stimulation, CD4+ T cells from mice infected with all the pathogens under study produced high levels of IFN-γ. IL-2 production was reduced in mice infected with Plasmodium species, but not with Listeria or Leishmania. In vitro blockade of the interaction between PD-1 and its ligands resulted in increased IFN-γ production in response to Plasmodium antigens, implying that PD-1 expressed on activated CD4+ T cells actively inhibit T cell immune responses. Studies using Myd88-/-, Trif-/-, and Irf3-/- mice showed that the induction of these CD4+ T cells and their ability to produce cytokines was largely independent of toll-like receptor signaling. These studies suggest that the expression of the inhibitory receptors, PD-1 and LAG-3 on CD4+ T cells and their reduced IL-2 production are common characteristic features of Plasmodium infection.
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http://naosite.lb.nagasaki-u.ac.jp/dspace/bitstream/10069/37062/1/ISYK859_Doe.pdf

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