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- Title
Expression of PD-1/LAG-3 and cytokine production by CD4<sup>+</sup> T cells during infection with Plasmodium parasites.
- Authors
Doe, Henrietta T.; Kimura, Daisuke; Miyakoda, Mana; Kimura, Kazumi; Akbari, Masoud; Yui, Katsuyuki
- Abstract
ABSTRACT CD4+ T cells play critical roles in protection against the blood stage of malarial infection; however, their uncontrolled activation can be harmful to the host. In this study, in which rodent models of Plasmodium parasites were used, the expression of inhibitory receptors on activated CD4+ T cells and their cytokine production was compared with their expression in 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, whereas 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 concentrations of IFN-γ. IL-2 production was reduced in mice infected with Plasmodium species, but not in those infected 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 inhibits T cell immune responses. Studies using Myd88−/−, Trif−/− and Irf3−/− mice showed that induction of these CD4+ T cells and their ability to produce cytokines is largely independent of TLR signaling. These studies suggest that 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.
- Subjects
PROGRAMMED cell death 1 receptors; CD4 antigen; LABORATORY rodents; PROTOZOAN diseases; PLASMODIUM yoelii; PLASMODIUM berghei; LISTERIA monocytogenes; LEISHMANIA major
- Publication
Microbiology & Immunology, 2016, Vol 60, Issue 2, p121
- ISSN
0385-5600
- Publication type
Article
- DOI
10.1111/1348-0421.12354