In vivo evidence of a functional association between immune cells in blood and brain in healthy human subjects

• Published in: Brain, behavior, and immunity Vol. 54; pp. 149 - 157
• Main Authors: Kanegawa, Naoki, Collste, Karin, Forsberg, Anton, Schain, Martin, Arakawa, Ryosuke, Jucaite, Aurelija, Lekander, Mats, Olgart Höglund, Caroline, Kosek, Eva, Lampa, Jon, Halldin, Christer, Farde, Lars, Varrone, Andrea, Cervenka, Simon
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.05.2016
• Subjects: [11C]PBR28; [C-11]PBR28; Adult; Age Factors; Allergy and Immunology; Biomarkers - blood; Biomarkers - metabolism; Blood immune cells; Blood-Brain Barrier - immunology; Blood-Brain Barrier - metabolism; Brain - immunology; Brain - metabolism; Carbon Radioisotopes - analysis; Cohort Studies; Female; Humans; Leukocyte Count; Male; Microglia; Microglia - immunology; Microglia - metabolism; Middle Aged; PET; Positron-Emission Tomography - methods; Protein Binding; Psychiatry; Radiopharmaceuticals - analysis; Receptors, GABA - blood; Receptors, GABA - immunology; Receptors, GABA - metabolism; Translocator protein; BBB; HAB; LAB; ROI; AUC; MAB; Microglia; Blood immune cells; Translocator protein; TAC; HCT; TSPO; [11C]PBR28; PET; VT; 18-kDa translocator protein; distribution volume; V T; high affinity binder; hematocrit value; mixed affinity binder; [ 11C]PBR28; area under the curve; low affinity binder; blood brain barrier; time activity curve; region of interest; positron emission tomography; [C]PBR28
• ISSN: 0889-1591; 1090-2139; 1090-2139
• DOI: 10.1016/j.bbi.2016.01.019

•We examined the immune cell marker TSPO in healthy human subjects using PET.•A strong positive correlation was observed between TSPO binding in brain and blood cells.•Associations were observed both at baseline and between two PET measurements.•Change in blood leukocyte counts was correlated to change in TSPO binding.•The results indicate an association between immunological cells in blood and brain. Microglia, the resident macrophages in the central nervous system, are thought to be maintained by a local self-renewal mechanism. Although preclinical and in vitro studies have suggested that the brain may contain immune cells also from peripheral origin, the functional association between immune cells in the periphery and brain at physiological conditions is poorly understood. We examined 32 healthy individuals using positron emission tomography (PET) and [11C]PBR28, a radioligand for the 18-kDa translocator protein (TSPO) which is expressed both in brain microglia and blood immune cells. In 26 individuals, two measurements were performed with varying time intervals. In a subgroup of 19 individuals, of which 12 had repeat examinations, leukocyte numbers in blood was measured on each day of PET measurements. All individuals were genotyped for TSPO polymorphism and categorized as high, mixed, and low affinity binders. We assessed TSPO binding expressed as total distribution volume of [11C]PBR28 in brain and in blood cells. TSPO binding in brain was strongly and positively correlated to binding in blood cells both at baseline and when analyzing change between two PET examinations. Furthermore, there was a significant correlation between change of leukocyte numbers and change in TSPO binding in brain, and a trend-level correlation to change in TSPO binding in blood cells. These in vivo findings indicate an association between immunological cells in blood and brain via intact BBB, suggesting a functional interaction between these two compartments, such as interchange of peripherally derived cells or a common regulatory mechanism. Measurement of radioligand binding in blood cells may be a way to control for peripheral immune function in PET studies using TSPO as a marker of brain immune activation.