Expression of PD-1/LAG-3 and cytokine production by CD4+T cells during infection with PlasmodiumparasitesExpression of PD-1/LAG-3 and cytokine production by CD4+T cells during infection with Plasmodiumparasites マラリア原虫感染におけるCD４＋T細胞のPD-1／LAG-3発現とサイトカイン産生の解析
131 , 2016-03-18 , John Wiley & Sons Australia, Ltd
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.
malaria CD4+ T cells inhibitory receptor cytokines
John Wiley & Sons Australia, Ltd
Thesis or Dissertation
Nagasaki University (長崎大学), 博士(医学) (2016-03-18)
(C) 2015 the Japanese Society for Bacteriology, the Japanese Society for Virology, the Japanese Society for Host Defense Research, and John Wiley & Sons Australia, Ltd. This is the peer reviewed version of the following article: Microbiology and Immunology, 60(2), pp.121-131; 2016, which has been published in final form at http://dx.doi.org/10.1111/1348-0421.12354. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.