Numerous studies have shown that motoneuron survival can be facilitated by neurotrophic factors (NTF) after injury. However, the ability of specific NTF to rescue facial motoneurons (FMN) from axotomy-induced death in immunodeficient mice has not been tested. Therefore, one goal of this study was to determine if brain-derived neurotrophic factor (BDNF), an NTF with a known ability to rescue FMN from axotomy-induced death, supports FMN from axotomy-induced death in recombinase activating gene-2 knockout (RAG-2 KO) mice that lack functional T and B lymphocytes. Nerve growth factor, which has been shown not to play a role in motoneuron survival, was used as a negative control. Brain derived neurotrophic factor treatment restored FMN survival to wild-type (WT) control levels 4 weeks post-operative (wpo) (80%±1.9, 83%±2.4, respectively). The second goal of this study was to begin to elucidate if CD4 + T cells produce NTF after facial nerve axotomy. Cervical lymph nodes were collected from WT mice 9 days post-operative, re-activated with anti-CD3 and supernatant collected 24h later. Immediately after injury, the supernatant was administered to RAG-2 KO mice leading to an increase in FMN survival equivalent to WT controls (80%±1.4, 84%±2.1, respectively, 4 wpo). In addition, cervical lymph node supernatant treated with anti-BDNF attenuated FMN rescue in RAG-2 KO mice (62%±3.3) 4 wpo. These data lend support to the hypothesis that CD4 + T cells produce NTF that support motoneuron survival before target reconnection occurs.