MHC class II enable murine activated CD8 T cells to directly interact with specific CD4 T cells

ROMAGNOLI PA; ALTMAN JD

Atlanta, GA

Simposio; Fifth Annual Graduate Student Research Symposium; 2007

Emory University

Immunological memory defines the ability of the immune system to respond effectively to a pathogen it has seen before. From all the cells that can be recalled upon a secondary challenge, memory CD8+ T cells are specially critical to control many viral infections. Intriguinly, CD8+ T cell differentiation into a memory cell has been shown to be dependant on CD4+ T cell help at the priming stage of the immune response. Several models for how CD4+ T cells provide help to CD8+ T cells have been proposed that involve a third, MajorHistocompatibility Complex (MHC) class II positive Antigen Presenting Cell(APC) as an intermediary. However, a three-cell cluster composed of a CD8+ Tcell, an APC and a CD4+ T cell is not a common event in a immune response.Therefore, we are proposing a model of CD8:CD4 T cell interaction facilitated by MHC class II molecules transferred onto activated CD8+ T cells from APCs. Here we show that MHC class II molecules are present on CD8+ T cells upon activation and that these molecules are transferred onto CD8+ T cells from APCs. MHC classII bearing activated CD8 T cells are then able to induce proliferation of antigen specific naïve CD4 T cells in vivo and restimulate in vitro differentiated CD4+ T cells to release IL2, IFNgamma and TNFalpha, cytokines involved in helping differentiation memory CD8+ T cell.These observations support a model of direct interaction between CD8+ and CD4+ T cells that might explain how help is delivered without the need of an intermediate APC. Moreover, these interactions not only can support the delivery of help, but also modulation of the immune response depending on which subpopulation of CD4+T cell is able to interact with the activated CD8+ T cell.