Effect of cerebellar fastigial nuclear lesions on differentiation and function of thymocytes

Abstract

We have previously shown that the cerebellum regulates functions of T, B and natural killer (NK) cells. Herein, we provide further evidence for cerebellar immunomodulation at the profiles of differentiation and maturation of thymocytes and function of mature T lymphocytes. Neuronal bodies of the fastigial nuclei (FN), one of three cerebellar nuclei, were damaged by microinjection of kainic acid (KA) in the bilateral FN. On days 12 and 32 following the KA injection, percentages of thymocyte subpopulations including CD4 −CD8 −, CD4 +CD8 +, CD4 +CD8 − and CD4 −CD8 + cells, apoptotic DNA fragmentation of thymocytes, and levels of interferon-γ (IFN-γ) and interleukin-4 (IL-4) in the serum were measured by flow cytometry, diphenylamine assay and enzyme-linked immunosorbent assay (ELISA), respectively. In the thymus, the percentage of CD4 +CD8 − cells in thymocyte population was elevated by the cerebellar FN lesions on both the 12th and the 32nd days post-lesion. The other thymocyte subsets only significantly changed at the late time point (day 32) post-lesion, with an increase in CD4 −CD8 − cells and a decrease in CD4 +CD8 + thymocytes relative to control rats with intact FN or saline-infused FN. The cerebellar FN lesions, regardless of the 12th or the 32nd day post-lesion, reduced the percentage of thymocyte DNA fragmentation and elevated the concentrations of IFN-γ and IL-4 in the serum. However, the cerebellar cortex lesions, as an additional control to show the specificity of the FN-lesion results, did not significantly alter the differentiation and apoptosis of thymocytes. These results reveal that the cerebellar FN lesions accelerate the differentiation of thymocytes into mature helper T lymphocytes in the thymus and enhance function of the helper T cells in the peripheral immune tissue. Collectively, these findings suggest a substantial modulation of immune system by the cerebellum.