CD4+T cell effector and regulatory subsets involved in rescuing facial motoneurons from axotomy -induced cell death

Motoneurons have regenerative capacity after peripheral nerve injury. However, the first requirement for the reparative process is neuronal survival. Therefore, a breakthrough in understanding motoneuron survival was the discovery that the CD4+ T immune cells, but not the CD8+ T, B or natural killer cells are critical to mediate facial motoneuron (FMN) survival after facial nerve axotomy. The objective of this dissertation was to identify CD4+ T cell subsets critical for mediating FMN survival after facial nerve axotomy. More specifically, the CD4+ T cell subsets that were tested included effector CD4+ T subsets, comprised of T helper (Th)1 and Th2 cells, and regulatory subsets comprised of CD4+CD25+ regulatory T and CD1-restricted NKT cells.;Investigation of the capacity of Th1 and/or Th2 cells to promote FMN survival after facial nerve axotomy was evaluated by identifying proteins critical for Th1 and Th2 differentiation that were involved in mediating FMN survival after facial nerve axotomy. Experimentation included analyzing cytokine expression from draining cervical lymph nodes after facial nerve axotomy and investigating whether cytokines and Signal Transducer and Activator of Transcription (STAT) proteins, involved in Th1 and Th2 differentiation and effector function, are also necessary to mediate FMN survival after facial nerve axotomy. The key findings from theses analyses are that the Th2 differentiation factor, STAT-6 is required for CD4+ T cell-mediated rescue of FMN from axotomy-induced cell death and that the Th2-associated cytokine, interleukin-4 is also critical for FMN survival, but that the Th1-associated proteins, STAT-4 and interferon-gamma are not. These findings not only suggest that the Th2 cell is critical to mediate FMN survival, but also begin to delineate the mechanisms by which CD4+ T cells mediate FMN survival after facial nerve axotomy.;Experimentation done to investigate the capacity of the CD4+ T regulatory subsets to mediate FMN survival after facial nerve axotomy suggest that neither CD4+CD25+ regulatory T nor NKT cells are critical to mediate FMN survival after facial nerve axotomy. The discovery that neither regulatory T cell subset is critical to mediate FMN survival further emphasizes the importance of the role of the Th2 effector subset, in mediating FMN survival after facial nerve axotomy.