scholarly journals Cytotoxic activities of CD8+ T cells collaborate with macrophages to protect against blood-stage murine malaria

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Takashi Imai ◽  
Hidekazu Ishida ◽  
Kazutomo Suzue ◽  
Tomoyo Taniguchi ◽  
Hiroko Okada ◽  
...  

The protective immunity afforded by CD8+ T cells against blood-stage malaria remains controversial because no MHC class I molecules are displayed on parasite-infected human erythrocytes. We recently reported that rodent malaria parasites infect erythroblasts that express major histocompatibility complex (MHC) class I antigens, which are recognized by CD8+ T cells. In this study, we demonstrate that the cytotoxic activity of CD8+ T cells contributes to the protection of mice against blood-stage malaria in a Fas ligand (FasL)-dependent manner. Erythroblasts infected with malarial parasites express the death receptor Fas. CD8+ T cells induce the externalization of phosphatidylserine (PS) on the infected erythroblasts in a cell-to-cell contact-dependent manner. PS enhances the engulfment of the infected erythroid cells by phagocytes. As a PS receptor, T-cell immunoglobulin-domain and mucin-domain-containing molecule 4 (Tim-4) contributes to the phagocytosis of malaria-parasite-infected cells. Our findings provide insight into the molecular mechanisms underlying the protective immunity exerted by CD8+ T cells in collaboration with phagocytes.

2001 ◽  
Vol 33 (1-2) ◽  
pp. 319 ◽  
Author(s):  
H Sun ◽  
V Subbotin ◽  
J Woodward ◽  
L Valdivia ◽  
J.J Fung ◽  
...  

1997 ◽  
Vol 42 (1) ◽  
pp. 225-232 ◽  
Author(s):  
Tsutao Takeshita ◽  
Yoshinori Fukui ◽  
Ken Yamamoto ◽  
Kazuaki Yamane ◽  
Takeshi Inamitsu ◽  
...  

Author(s):  
Xiaoguang Wang ◽  
Brittany C. Waschke ◽  
Rachel A. Woolaver ◽  
Samantha M. Y. Chen ◽  
Zhangguo Chen ◽  
...  

2002 ◽  
Vol 196 (12) ◽  
pp. 1627-1638 ◽  
Author(s):  
Laura Bonifaz ◽  
David Bonnyay ◽  
Karsten Mahnke ◽  
Miguel Rivera ◽  
Michel C. Nussenzweig ◽  
...  

To identify endocytic receptors that allow dendritic cells (DCs) to capture and present antigens on major histocompatibility complex (MHC) class I products in vivo, we evaluated DEC-205, which is abundant on DCs in lymphoid tissues. Ovalbumin (OVA) protein, when chemically coupled to monoclonal αDEC-205 antibody, was presented by CD11c+ lymph node DCs, but not by CD11c− cells, to OVA-specific, CD4+ and CD8+ T cells. Receptor-mediated presentation was at least 400 times more efficient than unconjugated OVA and, for MHC class I, the DCs had to express transporter of antigenic peptides (TAP) transporters. When αDEC-205:OVA was injected subcutaneously, OVA protein was identified over a 4–48 h period in DCs, primarily in the lymph nodes draining the injection site. In vivo, the OVA protein was selectively presented by DCs to TCR transgenic CD8+ cells, again at least 400 times more effectively than soluble OVA and in a TAP-dependent fashion. Targeting of αDEC-205:OVA to DCs in the steady state initially induced 4–7 cycles of T cell division, but the T cells were then deleted and the mice became specifically unresponsive to rechallenge with OVA in complete Freund's adjuvant. In contrast, simultaneous delivery of a DC maturation stimulus via CD40, together with αDEC-205:OVA, induced strong immunity. The CD8+ T cells responding in the presence of agonistic αCD40 antibody produced large amounts of interleukin 2 and interferon γ, acquired cytolytic function in vivo, emigrated in large numbers to the lung, and responded vigorously to OVA rechallenge. Therefore, DEC-205 provides an efficient receptor-based mechanism for DCs to process proteins for MHC class I presentation in vivo, leading to tolerance in the steady state and immunity after DC maturation.


2013 ◽  
Vol 4 ◽  
Author(s):  
Shin-Ichi Inoue ◽  
Mamoru Niikura ◽  
Shoichiro Mineo ◽  
Fumie Kobayashi

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Joshua M. Horne-Debets ◽  
Deshapriya S. Karunarathne ◽  
Rebecca J. Faleiro ◽  
Chek Meng Poh ◽  
Laurent Renia ◽  
...  

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