Mechanisms of maintenance CD8+ T cell memory responses (Memory Inflation) upon vaccination

• Applicant: Dr. Madeleine Elisabeth Zinser
• Subject Area: Gastroenterology
• Term: from 2016 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 290859236

Among long-lived CD8+ T cell memory populations, TEM and TCM are the two defined major subsets. Specific interest lies in long-lived TEM cells that are enhanced over time after certain viral infections such as CMV and, recently shown, upon adenoviral vaccination (memory inflation). They show strong functionality, vigorously proliferate upon restimulation and seem to share specific up- and downregulation of genes. Furthermore, it was shown that their development seems to depend on CD4+ T cell help. In this project we want to elucidate the magnitude, functionality and tissue localization of inflationary cells upon different routes of vaccination as well as after a prime boost regimen using a model antigen (beta-galactosidase) expressed on a human adenoviral vector (AdLac-Z) in C57BL/6 mice. Additionally, the role of CD4+ T cell help in the establishment of inflation needs to be further evaluated in early phases after vaccination and in prime-boost regimens as well as their possible inherent inflationary potential. Finally, the protective capacity of these long-lived T cell subsets is going to be evaluated in a murine systemic and mucosal challenge model.

• DFG Programme: Research Fellowships
• International Connection: United Kingdom
• Host: Professor Paul Klenerman, Ph.D.