Role of TGF‐β and PGE 2 in T cell responses during Plasmodium yoelii infection

• Published in: European journal of immunology 2007-06, Vol.37 (6), p.1562-1574
• Main Authors: Ocaña‐Morgner, Carlos, Wong, Kurt A., Lega, Flavia, Dotor, Javier, Borras‐Cuesta, Francisco, Rodriguez, Ana
• Format: Article
• Language: English
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.200737068

During an acute blood‐stage malaria infection, T cell responses to malaria and other bystander antigens are inhibited. Plasmodium infection induces strong cytokine responses that facilitate parasite clearance but may interfere with T cell functions, as some of the soluble immune mediators induced are also general inhibitors of T cell responses. Using a malaria mouse model, we have analyzed the cytokines produced by dendritic cells in response to P. yoelii infection that have potential T cell inhibitory activity. We found that during acute infection DC migrate to the spleen and secrete TGF‐β, prostaglandin E 2 (PGE 2 ) and IL‐10. We have analyzed the role of these general T cell inhibitors in a particular T cell response of evident importance in malaria infections: the CD8 + T cells generated against the liver‐stage of the disease. During blood‐stage infection, inhibition of the activity of TGF‐β and PGE 2 restores the CD8 + T cell responses generated by sporozoites, increasing protection against re‐infection. Our findings suggest that the strong cytokine response induced by blood‐stage P. yoelii infection affects host T cell responses, inhibiting protective CD8 + T cells against the liver‐stage of the disease.