In the past decades, interactions between the nervous system and the immune system have been well recognized and documented. While immune responses in the central nervous system (CNS) can have neurodestructive effects, accumulating data support a neuroprotective role as well. Our lab has previously shown that CD4⁺ T cells are critical for rescuing mouse facial motoneurons (FMN) from axotomy-induced cell death. Since CD4⁺ T cells have multiple subsets and secrete a wide spectrum of factors/cytokines, each subset may have a different role in the process of rescuing the injured neuron. Recently, our lab demonstrated that CD4⁺ T cells can make brain-derived neurotrophic factor (BDNF) and that BDNF is one of the critical mediators of CD4⁺ T cell-mediated neuroprotection. Furthermore, we revealed that T helper type 2 (Th2) cells, a subset of CD4⁺ T cells, are critical in rescuing FMN survival following facial nerve axotomy, indicating that the anti-inflammatory functions of CD4⁺ T cells also contribute to their neuroprotective effects. Therefore, I hypothesized that CD4⁺ T cells mediate neuroprotection via the production of the immunosuppressive cytokine, IL-10.

To test this hypothesis, I investigated the CD4⁺ T cell response [cytokine and neurotrophic factor (NTF) production] and the role of the inhibitory cytokine IL-10 in CD4⁺ T cell-mediated neuroprotection after facial nerve axotomy. The results indicate that both pro-inflammatory (Th1 and Th17) and anti-inflammatory CD4⁺ T cell subsets (Th2, Tr1 and Foxp3⁺ Treg) develop in the draining lymph nodes, with the peak at 7 days after axotomy. Axotomy increases the frequency of NTF-producing CD4⁺ T cells, and all differentiated CD4⁺ T cell subsets appear to have similar NTF-producing capacity. IL-10 deficiency potentiates axotomy-induced cell death, which can not be rescued by wild type CD4⁺ T cells. While CD4⁺ T cells and IL-10 are both required for FMN survival after facial nerve axotomy, CD4⁺ T cells are not the requisite source of the protective IL-10. CD4⁺ T cells may mediate neuroprotective effects directly by providing NTF and indirectly by increasing IL-10 production by resident glial cells within the CNS.