Schistosoma mansoni worms induce anergy of T cells via selective up-regulation of programmed death ligand 1 on macrophages

J Immunol. 2004 Jul 15;173(2):1240-8. doi: 10.4049/jimmunol.173.2.1240.


Infectious pathogens can selectively stimulate activation or suppression of T cells to facilitate their survival within humans. In this study we demonstrate that the trematode parasite Schistosoma mansoni has evolved with two distinct mechanisms to suppress T cell activation. During the initial 4- to 12-wk acute stages of a worm infection both CD4(+) and CD8(+) T cells are anergized. In contrast, infection with male and female worms induced T cell anergy at 4 wk, which was replaced after egg laying by T cell suppression via a known NO-dependent mechanism, that was detected for up to 40 wk after infection. Worm-induced anergy was mediated by splenic F4/80(+) macrophages (Mphi) via an IL-4-, IL-13-, IL-10-, TGF-beta-, and NO-independent, but cell contact-dependent, mechanism. F4/80(+) Mphi isolated from worm-infected mice were shown to induce anergy of naive T cells in vitro. Furthermore, naive Mphi exposed to live worms in vitro also induced anergy in naive T cells. Flow cytometry on in vivo and in vitro worm-modulated Mphi revealed that of the family of B7 costimulatory molecules, only programmed death ligand 1 (PD-L1) was selectively up-regulated. The addition of inhibitory mAb against PD-L1, but not PD-L2, to worm-modulated Mphi completely blocked the ability of these cells to anergize T cells. These data highlight a novel mechanism through which S. mansoni worms have usurped the natural function of PD-L1 to reduce T cell activation during early acute stages of infection before the subsequent emergence of egg-induced T cell suppression in the chronic stages of infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Differentiation / metabolism
  • B7-1 Antigen / biosynthesis
  • B7-1 Antigen / genetics
  • B7-H1 Antigen
  • Blood Proteins / biosynthesis
  • Blood Proteins / genetics
  • Cytokines / metabolism
  • Macrophages / metabolism*
  • Membrane Glycoproteins
  • Mice
  • Nitric Oxide / metabolism
  • Peptides / genetics
  • Schistosoma mansoni / immunology
  • Schistosoma mansoni / metabolism*
  • Schistosomiasis mansoni / immunology
  • Schistosomiasis mansoni / metabolism*
  • Spleen / metabolism
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*
  • Up-Regulation


  • Antigens, Differentiation
  • B7-1 Antigen
  • B7-H1 Antigen
  • Blood Proteins
  • Cd274 protein, mouse
  • Cytokines
  • Membrane Glycoproteins
  • Peptides
  • monocyte-macrophage differentiation antigen
  • Nitric Oxide