| To explore the role of peripheral immune cells associated with acquired immunity in neuronal survival after injury, the well-described facial nerve injury paradigm and the severe combined immunodeficient (scid) mouse model were combined. In scid mice, there is a gene mutation which blocks lymphocyte development and causes a lack of functional T and B lymphocytes. Recombinase-activating gene-2 knockout (RAG-2 KO), CD4 KO, CD8 KO, and B cell deficient (MμMT) mice were used to further characterize the peripheral immune systems role in neuronal survival. The first series of experiments in this dissertation demonstrated that normal FMN numbers were the same in all mouse types tested when comparing the non-axotomized left sides. Importantly, there were no differences found in FMN survival between the three different mouse strains used in this dissertation. Also, a significant decrease in FMN survival was observed in scid mice 4 wpo as compared to wild-type controls. Additionally, the results indicate that reconstituting scid mice with immunocompetent T and B cells prior to a facial nerve transection restored FMN survival to the level of wild-type mice. The next series of experiments demonstrated that CD4+ T lymphocytes, but not CD8+ T lymphocytes or B cells, mediate FMN survival after peripheral nerve injury.; In summary, the experiments in this dissertation addressed the proposal that CD4+ T cells mediate FMN survival after injury through the release of NTF. The results indicate that NTF are capable of rescuing FMN from axotomy-induced death in immunodeficient mice. Importantly, supernatant collected from re-activated T cells is capable of attenuating the axotomy-induced death observed in immunodefcient mice. The positive effects observed from the treatment of NTF and supernatant from re-activated T cells are also proposed to be transient. This effect is proposed to be due to the inability of the facial nerve to reconnect to its target tissue after a complete transection injury as utilized in this dissertation. These studies are the first to demonstrate that CD4+ T cells but not, CD8+ T cells, mediate neuronal survival after injury. Also, the B cell may not be critical for neuronal survival and an APC other than the B cell may be working in cooperation with the CD4+ T cell. Additionally, these data are the first to show that BDNF and GDNF, two NTF with a known ability to rescue FMN from axotomy-induced death support FMN survival after injury in immunodeficient mice. (Abstract shortened by UMI.)... |
