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Rationale The recently discovered meningeal lymphatic vessels (mLVs) have been proposed to be the missing link between the immune and the central nervous systems. The role of mLVs in modulating the neuro-immune response following a brain injury, however, has not been analyzed. Parenchymal T lymphocyte infiltration has been previously reported as part of secondary events after traumatic brain injury (TBI), suggestive of an adaptive neuro-immune response. The phenotype of these cells has remained uncharacterized. In this study, we identified the subpopulations of T cells infiltrating the perilesional areas 30 days post-injury (an early-chronic time point). Furthermore, we analyzed how the lack of mLVs affects the magnitude and the type of immune response in the brain after TBI. Methods TBI was induced in K14-VEGFR3-Ig mice (lacking mLVs), or in their littermate controls (WT), applying a controlled cortical impact (CCI). One month after TBI, T cells were isolated from cortical areas ipsilateral or contralateral to the trauma and from the spleen, and analyzed by flow cytometry for TCRβ (T cells), CD4 (T-helper cells), CD8 (cytotoxic T cells), CD44 (memory T cells), and CD69 (effector T cells). Lesion size in each animal was evaluated by MRI. Results In both WT- and K14-VEGFR3-Ig-CCI mice, we found a prominent T cell infiltration in the brain, confined to the perilesional cortex and hippocampus. The majority of infiltrating T cells are CD8+ (cytotoxic T cells), expressing a CD44 hi CD69+ phenotype, suggesting that these are effector resident memory T cells. K14-VEGFR3-Ig mice showed a significant reduction of infiltrating CD4+ T lymphocytes, implying that mLVs are important in establishing a proper neuro-immune response. Negligible T cell infiltration was observed in the contralateral unaffected side. Extension of the lesion (measured as lesion volume from MRI) did not differ between the genotypes. Finally, TBI did not correlate with alterations in peripheral circulating T cells, as assessed one month after injury induction. Conclusions Our data support the hypothesis that mLVs are pivotal for a proper and specific neuro-immune response after TBI, which is principally mediated by the resident memory cytotoxic CD8+ T cells. |
