RGD Reference Report - Depletion of regulatory T cells increases T cell brain infiltration, reactive astrogliosis, and interferon-γ gene expression in acute experimental traumatic brain injury. - Rat Genome Database

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Depletion of regulatory T cells increases T cell brain infiltration, reactive astrogliosis, and interferon-γ gene expression in acute experimental traumatic brain injury.

Authors: Krämer, Tobias J  Hack, Nathalia  Brühl, Till J  Menzel, Lutz  Hummel, Regina  Griemert, Eva-Verena  Klein, Matthias  Thal, Serge C  Bopp, Tobias  Schäfer, Michael K E 
Citation: Krämer TJ, etal., J Neuroinflammation. 2019 Aug 5;16(1):163. doi: 10.1186/s12974-019-1550-0.
RGD ID: 124715446
Pubmed: PMID:31383034   (View Abstract at PubMed)
PMCID: PMC6683516   (View Article at PubMed Central)
DOI: DOI:10.1186/s12974-019-1550-0   (Journal Full-text)


BACKGROUND: Traumatic brain injury (TBI) is a major cause of death and disability. T cells were shown to infiltrate the brain during the first days after injury and to exacerbate tissue damage. The objective of this study was to investigate the hitherto unresolved role of immunosuppressive, regulatory T cells (Tregs) in experimental TBI.
METHODS: "Depletion of regulatory T cell" (DEREG) and wild type (WT) C57Bl/6 mice, treated with diphtheria toxin (DTx) to deplete Tregs or to serve as control, were subjected to the controlled cortical impact (CCI) model of TBI. Neurological and motor deficits were examined until 5 days post-injury (dpi). At the 5 dpi endpoint, (immuno-) histological, protein, and gene expression analyses were carried out to evaluate the consequences of Tregs depletion. Comparison of parametric or non-parametric data between two groups was done using Student's t test or the Mann-Whitney U test. For multiple comparisons, p values were calculated by one-way or two-way ANOVA followed by specific post hoc tests.
RESULTS: The overall neurological outcome at 5 dpi was not different between DEREG and WT mice but more severe motor deficits occurred transiently at 1 dpi in DEREG mice. DEREG and WT mice did not differ in the extent of brain damage, blood-brain barrier (BBB) disruption, or neuronal excitotoxicity, as examined by lesion volumetry, immunoglobulin G (IgG) extravasation, or calpain-generated αII-spectrin breakdown products (SBDPs), respectively. In contrast, increased protein levels of glial fibrillary acidic protein (GFAP) and GFAP+ astrocytes in the ipsilesional brain tissue indicated exaggerated reactive astrogliosis in DEREG mice. T cell counts following anti-CD3 immunohistochemistry and gene expression analyses of Cd247 (CD3 subunit zeta) and Cd8a (CD8a) further indicated an increased number of T cells infiltrating the brain injury sites of DEREG mice compared to WT. These changes coincided with increased gene expression of pro-inflammatory interferon-γ (Ifng) in DEREG mice compared to WT in the injured brain.
CONCLUSIONS: The results show that the depletion of Tregs attenuates T cell brain infiltration, reactive astrogliosis, interferon-γ gene expression, and transiently motor deficits in murine acute traumatic brain injury.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
traumatic brain injury  ISOCd8a (Mus musculus)124715446; 124715446mRNA:increased expression:brain (mouse)RGD 
traumatic brain injury  IEP 124715446mRNA:increased expression:brain (mouse)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Cd8a  (CD8 subunit alpha)

Genes (Mus musculus)
Cd8a  (CD8 subunit alpha)

Genes (Homo sapiens)
CD8A  (CD8 subunit alpha)


Additional Information