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

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)-alpha is a cytokine with manifold effects on the neuroimmune system. Specific TNF-alpha receptors have been found on human peripheral blood lymphocytes. The aim of the present study has been to assay TNF-alpha 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-alpha receptors than those from controls (Bmax: 705, 29 vs 131, 6 (mean, SEM) receptors/cell). Such TNF-alpha binding sites, of the same type in DAT patients and healthy subjects (Kd: 67.6, 5.0 vs 70.7, 5.6 (mean, SEM) pM), are functional, since they are able to mediate in vitro NF-kappa B activation. These results are discussed in terms of DAT pathogenesis. Since it has been reported that activated T cells have more TNF-alpha receptors than resting cells, an increased number of lymphocyte TNF-alpha receptors might indicate a systemic immune activation in DAT patients as compared with healthy controls.