Rejuvenation of thymus and modulation of local and systemic T cell responses in animal model of Alzheimer's disease following cell therapy using sperm head.

In Alzheimer's disease (AD), the balance of T cell response in the brain is dysregulated due to increase of T-helper 1 (Th1) and Th17 over Th2 response. Considering the link between local and systemic immune response, it is important to modulate brain pattern of T cell in harmony with the systemic immune system. Some studies also attempted to rejuvenate thymus which is affected in AD. Based on immunologic properties of sperm, previous studies demonstrated significant therapeutic effects of sperm head on the brain AD animal models. In this study, pattern of T cell response was determined locally in the brain and systemically in the cervical lymph nodes, and spleen. Thymus health status was also evaluated using forkhead box N1 (FOXN1). The results were compared between control and sperm head-treated AD model animals. In the brain, cervical lymph nodes, and spleen, treatment with sperm head significantly decreased interferon-gamma (IFN-γ) along with interleukin-17 (IL-17) and increased IL-4, representative of Th1, Th17, and Th2, respectively. Surprisingly, in the sperm head-treated AD model animals, significant decrease was observed in regulatory T cells (Treg), represented by cluster of designation 4 (CD4), CD25, and FOXP3 high expression. Interestingly, sperm head had significant rejuvenation effects on the thymus represented by increase in FOXN1. The results show that sperm head could deviate chronic inflammation towards a constructive inflammation. Results suggest revision of our attitude towards the inflammation as the results suggest that boosting inflammation can be more efficient than suppressing inflammation for treatment of AD.