| First Author | Butler NS | Year | 2010 |
| Journal | J Immunol | Volume | 184 |
| Issue | 5 | Pages | 2528-38 |
| PubMed ID | 20097864 | Mgi Jnum | J:159666 |
| Mgi Id | MGI:4452216 | Doi | 10.4049/jimmunol.0903529 |
| Citation | Butler NS, et al. (2010) Differential effector pathways regulate memory CD8 T cell immunity against Plasmodium berghei versus P. yoelii sporozoites. J Immunol 184(5):2528-38 |
| abstractText | Malaria results in >1,000,000 deaths per year worldwide. Although no licensed vaccine exists, much effort is currently focused on subunit vaccines that elicit CD8 T cell responses directed against Plasmodium parasite liver stage Ags. Multiple immune-effector molecules play a role in antimicrobial immunity mediated by memory CD8 T cells, including IFN-gamma, perforin, TRAIL, Fas ligand, and TNF-alpha. However, it is not known which pathways are required for memory CD8 T cell-mediated immunity against liver stage Plasmodium infection. In this study, we used a novel immunization strategy to generate memory CD8 T cells in the BALB/c mouse model of P. berghei or P. yoelii sporozoite infection to examine the role of immune-effector molecules in resistance to the liver stage infection. Our studies reveal that endogenous memory CD8 T cell-mediated protection against both parasite species is, in part, dependent on IFN-gamma, whereas perforin was only critical in protection against P. yoelii. We further show that neutralization of TNF-alpha in immunized mice markedly reduces memory CD8 T cell-mediated protection against both parasite species. Thus, our studies identify IFN-gamma and TNF-alpha as important components of the noncytolytic pathways that underlie memory CD8 T cell-mediated immunity against liver stage Plasmodium infection. Our studies also show that the effector pathways that memory CD8 T cells use to eliminate liver stage infection are, in part, Plasmodium species specific. |
