The adoptive transfer of BCG-induced T lymphocytes contributes to hippocampal cell proliferation and tempers anxiety-like behavior in immune deficient mice

Abstract

We previously have reported that neonatal Bacillus Calmette-Guerin (BCG) vaccination improves neurogenesis and behavior in early life through affecting the neuroimmune milieu in the brain, but it is uncertain whether activation phenotypes and functional changes in T lymphocytes shape brain development. Here, we studied the effects of BCG vaccination via the adoptive transfer of T lymphocytes from the BALB/c wild-type mice into naive mice. Our results show that mice adoptive BCG-induced lymphocytes (BCG->naive mice) showed anxiolytic and antidepressant-like performance when completing an elevated plus maze (EPM) test. Meanwhile, BCG->naive mice possess more cell proliferation and newborn neurons than PBS->naive and nude mice in the hippocampus. IFN-γ and IL-4 levels in the serum of BCG

Toll-like receptors 2 and 4 differentially regulate the self-renewal and differentiation of spinal cord neural precursor cells

“…Complex cell-autonomous and non-cell-autonomous mechanisms operate concomitantly with the involvement of TLR-dependent signaling [ 61 , 62 ]. While studies have demonstrated that immune-deficient mice, with limited TLR activation, show impaired neurogenesis and that specific T helper cells, TLR activators, promote neurogenesis in the adult hippocampus [ 63 ], TLR4 has been linked to spontaneous oligodendrocyte maturation and remyelination after damage in an inflammatory environment, such as after SCI [ 27 ]. Well-orchestrated adaptive immune responses can also support/induce oligodendrogenesis and neurogenesis.…”

COVID-19 vaccination may enhance hippocampal neurogenesis in adults

“…In contrast, the vaccination induces a (CD4+) T helper-1 (Th1) cell-mediated adaptive immune response, added with the M2 microglial activation, thus causing elevated levels of the anti-inflammatory cytokines, such as interferon (IFN)-γ, interleukin (IL)-4, transforming growth factor (TGF)-β, which promote proliferation and differentiation of the NSCs (Fig. Ib) ( Qi et al, 2017 , Qi et al, 2016 , Song et al, 2020 , Xia et al, 2014 , Yang et al, 2016 ). The vaccination also induces elevated levels of neurotrophic molecules, such as BDNF and insulin-like growth factor (IGF)-1, which can further promote AHN ( Qi, 2015 ).…”

“…There is substantial empirical evidence supporting the potential neurotrophic influence of the COVID-19 vaccination. Noteworthy to mention is the animal model studies showing the effects of vaccinations against respiratory tract infections such as influenza and tuberculosis ( Qi et al, 2017 , Qi et al, 2016 , Song et al, 2020 , Xia et al, 2014 , Yang et al, 2016 ).…”

“…IFN-γ and IL-4 levels in the serum of BCG vaccinated naive mice also increased; in contrast, TNF-α and IL-1β levels reduced. The alterations in ratios of splenic CD4+ and CD8+ memory T cells most likely affected the expression of correlative cytokines in the serum, accounting for the shift in behavioral results ( Song et al, 2020 ).…”

“…Notably, these studies showed considerable enhancement of hippocampus-dependent cognitive functions, such as working memory and spatial learning abilities, in the vaccinated animals. ( Qi et al, 2017 , Qi et al, 2016 , Song et al, 2020 , Xia et al, 2014 , Yang et al, 2016 ).…”