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. The molecular basis for CD4+ T cell help for CD8+ T cell memory is however poorly understood.
We hypothesize that this CD4+ T cell help for CD8+ T cell memory is provided via 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 are currently investigating how CD4+ T cells might imprint DCs to maintain effective 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:
- 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.
- 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.
- Kara Bickham and Christian Münz, "Contrasting roles of dendritic cells and B cells in the immune control of Epstein-Barr virus", Current topics in Microbiology and Immunology (2003), 276: 55-76.