Interaction with antigen-specific T cells regulates expression of the lactate transporter MCT1 in primary rat astrocytes: specific link between immunity and homeostasis.
Monocarboxylates like lactate are provided by astrocytes and can be used as fuel by neurons and oligodendrocytes. In an autoimmune inflammatory environment, homeostatic functions of astrocytes are incompletely understood. In primary Lewis rat astrocytes, co-culture with MHC class II-restricted myelin basic protein (MBP)-specific T cells in the presence of MBP resulted in a marked upregulation of the astrocytic lactate transporter MCT1 that is to export lactate into the extracellular space. It was evident that the increase in MCT1 was triggered by T cells in an antigen-dependent manner. The glial isoform of the glucose transporter GLUT1 was not regulated under these conditions. T-cell blasts that had been pre-activated by antigen and splenic antigen-presenting cells (APCs) beforehand also led to an increase in the expression of astrocytic MCT1 after co-culture. Resting T cells did not induce a relevant upregulation of MCT1 in astrocytes. However, resting T cells stimulated the expression of MCT1 when anti-MHC class II antibodies, but not when anti-MHC class I antibodies, were added to the co-culture. Therefore, even in the presence of inactive T cells, complexation of MHC class II molecules on astrocytes might lead to the regulation of certain astrocytic transport proteins. Consistent with the in vitro experiments, an upregulation of MCT1 was observed in the spinal cord of autoimmune encephalitic rats while GLUT1 expression appeared to be unchanged. This T-cell-mediated regulation of MCT1 might contribute to a compensatory or protective mechanism in order to guarantee substrate pools for neurons and oligodendrocytes under inflammatory conditions.
Korn
Thomas
T
Department of Neurology, Universität des Saarlandes, Homburg, Germany. netkor@uniklinik-saarland.de
Magnus
Tim
T
Jung
Stefan
S
D019264:Adoptive Transfer; D000818:Animals; D000906:Antibodies / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology; D001253:Astrocytes / Q000276:immunology* / Q000378:metabolism; D051926:Basigin; D002450:Cell Communication / Q000276:immunology*; D002478:Cells, Cultured; D002490:Central Nervous System / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D018920:Coculture Techniques; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D027342:Excitatory Amino Acid Transporter 2 / Q000378:metabolism; D006168:Guinea Pigs; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006706:Homeostasis / Q000276:immunology; D007109:Immunity / Q000276:immunology; D019344:Lactic Acid / Q000378:metabolism; D027501:Monocarboxylic Acid Transporters / Q000378:metabolism*; D004676:Myelin Basic Protein / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D027981:Symporters / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology*; D015854:Up-Regulation / Q000276:immunology; D000099233:Monocarboxylate Transport Protein 1
D000906:Antibodies; D015703:Antigens, CD; D051926:Basigin; D027342:Excitatory Amino Acid Transporter 2; D000949:Histocompatibility Antigens Class II; D019344:Lactic Acid; D027501:Monocarboxylic Acid Transporters; D004676:Myelin Basic Protein; D027981:Symporters; D000099233:Monocarboxylate Transport Protein 1