ABSTRACT
Despite the blood-brain barrier (BBB) the human CNS is continuously screened by blood-derived immunological cells. In certain brain areas the local BBB configuration grants passage of large molecules, whereas others are better shielded. We investigated whether these regional BBB compositions are paralleled by differences in the degree of cellular immunosurveillance by investigating tissue from 23 normal human brains for several CD markers, FoxP3, granzyme B, and perforin. Our results provide evidence that immunosurveillance is associated with locoregional BBB configuration and is mainly performed by CD3(+)/CD8(+)/granzyme B(-)/perforin(-) lymphocytes.
Subject(s)
Blood-Brain Barrier/immunology , CD8-Positive T-Lymphocytes/immunology , Central Nervous System/blood supply , Central Nervous System/immunology , Adult , Age Factors , Aged , Blood-Brain Barrier/cytology , CD3 Complex/metabolism , CD8 Antigens/metabolism , CD8-Positive T-Lymphocytes/metabolism , Central Nervous System/cytology , Female , Humans , Immunohistochemistry , Immunophenotyping , Male , Middle Aged , Sex Factors , Young AdultABSTRACT
HLA-E is a ligand for the immune-inhibitory NKG2A receptor expressed on NK and T cells. To investigate HLA-E expression and immune cell infiltration in human astrocytic tumors in vivo, we analyzed normal CNS controls and astrocytomas of all WHO grades by immunohistochemistry. Both, CD8(+) immune cell infiltration and HLA-E expression were significantly higher in astrocytic tumors than in normal brain. Further, HLA-E expression levels and immune cell infiltration were significantly correlated in WHO grade IV glioblastomas. Thus, HLA-E overexpression in glioblastomas may be triggered by T and NK cell infiltration.
Subject(s)
Astrocytoma/metabolism , Brain Neoplasms/metabolism , CD8-Positive T-Lymphocytes/physiology , Gene Expression Regulation, Neoplastic/physiology , Glioblastoma/metabolism , HLA Antigens/metabolism , Histocompatibility Antigens Class I/metabolism , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , HLA-E AntigensABSTRACT
Immunohistochemical procedures constitute a high methodological value in both pathologic diagnostics and research. Staining quality depends on a large variety of interference factors. Primarily, background staining reduces the quality of evaluation by reducing the chromatic discrimination. For the identification of important interference factors, various incubation steps and composition of solutions recommended in routine protocols were altered or omitted in our study. Surprisingly, the most important effect concerning background staining reduction could be significantly attributed to the omission of albumin which usually is recommended as a reducer of background stainings. However, in contrast to this negative effect, albumin could also increase specific staining intensity. These findings lead to the recommendation of a careful use of albumin in immunohistochemistry because of the dichotomous effects mentioned above. Furthermore, these results imply that in case of a good specific staining pattern, the use of albumin in immunohistochemical solutions merely exerts significant negative background staining effects.
