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

Song, D.; Qi, F.; Liu, S.; Tang, Z.; Duan, J.; Yao, Z. B.

doi:10.1101/844704

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bioRxiv · 10.1101/844704

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

Song, D.·Qi, F.·Liu, S.·Tang, Z.·Duan, J.·Yao, Z. B.

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Abstract

1.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-{gamma} and IL-4 levels in the serum of BCG->naive mice also increased, while TNF- and IL-1{beta} levels were reduced relative to those of PBS->naive and nude mice. We further found that BCG->naive mice showed different repartition of CD4+ and CD8+ T cell to naive (CD62L+ CD44low), effector memory (CD62L- CD44hi), central memory (CD62L+ CD44hi) and acute/activated effector (CD62L- CD44low) cells in the spleen. Importantly, the adoptive transfer of BCG-induced T lymphocytes infiltrated into the dura mater and brain parenchyma of the nude mice. Activation phenotypes and functional changes in T lymphocytes are very likely to affect the neuroimmune milieu in the brain, and alterations in ratios of splenic CD4+ and CD8+ memory T cells may affect the expression of correlative cytokines in the serum, accounting for our behavioral results. We conclude thus that the adoptive transfer of BCG-induced T lymphocytes contributes to hippocampal cell proliferation and tempers anxiety-like behavior in immune deficient mice. Our work shows that BCG vaccination improves hippocampal cell proliferation outcomes and behaviors, likely as a result of splenic effector/memory T lymphocytes regulating the neuroimmune niche in the brain.

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Song, D., Qi, F., Liu, S., Tang, Z., Duan, J., Yao, Z. B.. 2019-11-15. The adoptive transfer of BCG-induced T lymphocytes contributes to hippocampal cell proliferation and tempers anxiety-like behavior in immune deficient mice. https://doi.org/10.1101/844704

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