EBV specific CD8+ T cell memory
It is widely believed that chronic infections can only be controlled after establishment of good T cell memory. Memory CD8+ T cells can promptly expand and mediate rapidly effector functions to counteract reactivation of persistent pathogens. CD8+ T cell memory crucially depends on CD4+ T cell help. In fact persistent infections cannot be controlled in the absence of CD4+ T cells.
We hypothesize that this CD4+ T cell help for CD8+ T cell memory is best established by stimulation with dendritic cells (DCs). We could demonstrate that DCs cross-present EBV antigens to CD4+ as well as CD8+ T cells from dead EBV transformed B cells. This pathway establishes protective immunity against EBV transformed B cells in vitro, while EBV transformed B cells are unable to prime EBV specific T cells in vitro. We have also demonstrated that DCs are more potent than EBV transformed B cells in restimulating EBV specific CD8+ T cells.
We are currently investigating how EBV infection imprints DCs to establish effective CD4+ and CD8+ T cell memory and which characteristics EBV specific memory T cells have. Since EBV infection is exceptionally well controlled in the majority of infected individuals, this analysis might reveal the memory CD8+ T cell phenotype that has to be generated to control other persistent infections or tumors.
Related articles from our laboratory:
1. Marion Subklewe, Casper Paludan, Ming L. Tsang, Karsten Mahnke, Ralph M. Steinman and Christian Münz
Dendritic cells cross-present latency gene products from Epstein-Barr virus transformed B cells and expand tumor-reactive CD8+ killer T cells. Journal of Experimental Medicine (2001), 193: 405-411
2. Kara Bickham, Kiera Goodman, Casper Paludan, Sarah Nikiforow, Ming L. Tsang, Ralph M. Steinman and Christian Münz
Dendritic cells initiate immune control of Epstein Barr virus transformation of B lymphocytes in vitro. Journal of Experimental Medicine (2003), 198:1653-1663
3. Marion Subklewe, Kathrin Sebelin, Andrea Block, Antje Meier, Anna Roukens, Casper Paludan, Jean-Francois Fonteneau, Ralph M. Steinman and Christian Münz
Dendritic cells expand Epstein-Barr virus specific CD8+ T cell responses more efficiently than EBV transformed B cells. Human Immunology (2005), 66: 938-949
4. Kevin Heller, Beza Seyoum, Jenica Upshaw, Henry Zebroski and Christian Münz
Distinct memory CD4+ T cell subsets mediate immune recognition of Epstein Barr virus nuclear antigen 1 in healthy virus carriers. Blood (2007), 109: 1138-1146
5. Jan D. Lünemann, Ilijas Jelcic, Susanne Roberts, Andreas Lutterotti, Björn Tackenberg, Roland Martin and Christian Münz
EBNA1-specific T cells from patients with multiple sclerosis cross-react with myelin antigens and co-produce IFN-gamma and interleukin-2. Journal of Experimental Medicine (2008), 205: 1763-1773