The goal of this study is to examine how ongoing acute and chronic infections and exposure to tumors affect naive bystander T cell populations. It is hypothesized that the environment a naive T cell is exposed to prior to T cell receptor specific activation will affect its ability to respond to antigen.
The specific aims are to analyze the status, kinetics, and stability of naive T cells during acute and chronic infections and to determine how chronic antigen exposure during persistent infections or persisting tumors has on the ability of bystander naive T cells to mount immune responses. In addition, to determine the effect of introducing therapeutic cytokines during a chronic infection or tumor model has on bystander naive T cells. Using a TCR transgenic model we will expose, by adoptive transfer, OVA TCR naive T cells to acute LCMV, chronic LCMV infection or Lewis Lung Carcinoma tumor transplant model. Recovered OVA naive cells will then be adoptively transferred into normal LCMV immune recipients to determine their ability to respond to OVA infection. This study will give clues in the development and timing of therapies and will lead to therapeutic developments for targeting naive T cell viability during chronic diseases and immune suppression.
| Premenko-Lanier, Mary; Moseley, Nelson B; Pruett, Sarah T et al. (2008) Transient FTY720 treatment promotes immune-mediated clearance of a chronic viral infection. Nature 454:894-8 |
