T-cell tumour necrosis factor-α receptor binding in demented patients

Abstract

Dementia of Alzheimer type (DAT) is a neurodegenerative disease of the central nervous system (CNS), in which an unbalanced cytokine network may lead to an altered immunoregulation. Tumour necrosis factor (TNF)-α is a cytokine with manifold effects on the neuroimmune system. Specific TNF-α receptors have been found on human peripheral blood lymphocytes. The aim of the present study has been to assay TNF-α binding on T cells from DAT patients and healthy sex- and age-matched controls. We found that T lymphocytes from demented patients bear significantly more p60 and p80 TNF-α receptors than those from controls (B_max: 705, 29 vs 131, 6 (mean, SEM) receptors/cell). Such TNF-α binding sites, of the same type in DAT patients and healthy subjects (K_d: 67.6, 5.0 vs 70.7, 5.6 (mean, SEM) pM), are functional, since they are able to mediate in vitro NF-κB activation. These results are discussed in terms of DAT pathogenesis. Since it has been reported that activated T cells have more TNF-α receptors than resting cells, an increased number of lymphocyte TNF-α receptors might indicate a systemic immune activation in DAT patients as compared with healthy controls.