No evidence for generation of Th-2-like MBP-specific T-cell lines by blockade of the costimulatory molecule B7-1.
The T helper-1 (Th-1)/T helper-2 (Th-2) paradigm is relevant for the pathogenesis and therapy of multiple sclerosis. In experimental autoimmune encephalomyelitis, a shift towards a Th-2 immune response serves as treatment of the disease. In the human immune system, the factors which determine and modulate the differentiation of CD4+ T cells into the Th-1 or Th-2 phenotype have yet to be elucidated completely. Here, the split-well approach was used to analyse costimulatory requirements for the generation of myelin basic protein-specific T-cell subsets considered to play a major role in the pathogenesis of multiple sclerosis. Myelin basic protein-specific T-cell lines were isolated from peripheral blood cells of healthy individuals in the presence or absence of a blockade of the costimulatory molecule B7-1, previously reported to be involved in the development of Th-1 cells. T-helper type was determined by the interferon/interleukin ratio. Blockade of B7-1 did not increase the number of Th-2-like myelin basic protein-specific T-cell lines. Thus, these data show no evidence for an influence of B7-1 blockade on the development of human myelin basic protein-specific T-cell subsets. These results have to be taken into account when discussing whether antibody-mediated B7-1 blockade might be a suitable therapy in multiple sclerosis, as demonstrated in experimental autoimmune encephalomyelitis.
Zipp
F
F
Department of Neurology, Charité, Berlin, Germany. frauke.zipp@charite.de
D000276:Adjuvants, Immunologic / Q000037:antagonists & inhibitors; D018122:B7-1 Antigen / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D009103:Multiple Sclerosis / Q000209:etiology* / Q000276:immunology; D004676:Myelin Basic Protein / Q000276:immunology*; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology*; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology*
D000276:Adjuvants, Immunologic; D018122:B7-1 Antigen; D004676:Myelin Basic Protein