Functional changes in astrocytes by human T-lymphotropic virus type-1 T-lymphocytes

The human T-lymphotropic virus type-1 (HTLV-1) is the causative agent of a chronic progressive myelopathy (TSP/HAM) in which lesions of the central ne rvous system (CNS) are associated with infiltration of HTLV-1-infected T-ce lls. In a model that mimics the interaction between glial and T-cells, we s how that transient contact with T-lymphocytes chronically infected with HTL V-1 induce profound metabolic alterations in astrocytes. Within the first w eek post-contact, an overall activation of astrocyte metabolism was observe d as assessed by enhanced uptake of glutamate and glucose, and lactate rele ase. In contrast, longer examination showed a reduced astrocytic accumulati on of glutamate. The time course of the change in glutamate uptake was in f act biphasic. Previous observations indicated that HTLV-1 protein Tax-1 was involved in this delayed decrease, via the induction of TNF-alpha. The exp ression of the glial glutamate transporters, GLAST and GLT-1 decreased in p arallel. These decreases in glutamate uptake and transporters' expression w ere associated with an imbalance in the expression of the catabolic enzymes of glutamate, GS and GDH, presumably due to Tax-1. Given the fact that imp airment of glutamate management in astrocytes is able to compromise the fun ctional integrity of neurons and oligodendrocytes, our results altogether g ive new insights into the physiopathology of TSP/HAM. (C) 2001 Elsevier Sci ence BN. All rights reserved.