Differential expression of major histocompatibility complex class I in developmental glioneuronal lesions.
OBJECTIVE
The expression of the major histocompatibility complex class I (MHC-I) in the brain has received considerable interest not only because of its fundamental role in the immune system, but also for its non-immune functions in the context of activity-dependent brain development and plasticity.


METHODS
In the present study we evaluated the expression and cellular pattern of MHC-I in focal glioneuronal lesions associated with intractable epilepsy. MHC-I expression was studied in epilepsy surgery cases with focal cortical dysplasia (FCD I, n = 6; FCD IIa, n = 6 and FCD IIb, n = 15), tuberous sclerosis complex (TSC, cortical tubers; n = 6) or ganglioglioma (GG; n = 15) using immunocytochemistry. Evaluation of T lymphocytes with granzyme-B+ granules and albumin immunoreactivity was also performed.


RESULTS
All lesions were characterized by MHC-I expression in blood vessels. Expression in both endothelial and microglial cells as well as in neurons (dysmorphic/dysplastic neurons) was observed in FCD II, TSC and GG cases. We observed perivascular and parenchymal T lymphocytes (CD8+, T-cytotoxic) with granzyme-B+ granules in FCD IIb and TSC specimens. Albumin extravasation, with uptake in astrocytes, was observed in FCD IIb and GG cases.


CONCLUSIONS
Our findings indicate a prominent upregulation of MHC-I as part of the immune response occurring in epileptogenic glioneuronal lesions. In particular, the induction of MHC-I in neuronal cells appears to be a feature of type II FCD, TSC and GG and may represent an important accompanying event of the immune response, associated with blood-brain barrier dysfunction, in these developmental lesions.
Department of Neuro Pathology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, Amsterdam 1105 AZ, The Netherlands. e.aronica@amc.uva.nl
Avanita S
AS
Prabowo
Anand M
AM
Iyer
Jasper J
JJ
Anink
Wim G M
WG
Spliet
Peter C
PC
van Rijen
Eleonora
E
Aronica
D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology*; D005805:Genes, MHC Class I / Q000276:immunology*; D006801:Humans; D008285:Major Histocompatibility Complex / Q000276:immunology; D008297:Male; D017628:Microglia / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D014402:Tuberous Sclerosis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D055815:Young Adult