ORGAN-SPECIFIC AUTOANTIGENS INDUCE TRANSFORMING GROWTH-FACTOR-BETA MESSENGER-RNA EXPRESSION IN MONONUCLEAR-CELLS IN MULTIPLE-SCLEROSIS AND MYASTHENIA-GRAVIS

Multiple sclerosis (MS) is characterized by patchy accumulations of in flammatory cells combined with demyelination. There are mononuclear ce lls in blood and cerebrospinal fluid of patients with MS that produce interferon-gamma and interleukin-4 in response to myelin basic protein (MBP) and proteolipid protein (PLP). Here we describe autoantigen-ind uced production of transforming growth factor-beta (TGF-beta). This mu ltifunctional cytokine has inhibitory effects on the growth, different iation, and effector functions of activated T cells. Blood and cerebro spinal fluid cells were exposed in short-term cultures to MBP and PLP and, after hybridization with complementary DNA oligonucleotide probes , they were evaluated for TGF-beta mRNA expression, Patients with MS h ad higher numbers of MBP- and PLP-responsive TGF-beta mRNA expressing cells in blood compared with control patients with other neurological diseases or myasthenia gravis and a five- and threefold further increm ent in their cerebrospinal fluid. In blood of patients with myasthenia gravis, where the acetylcholine receptor (AChR) isa target for autoag gressive immunity, there were increased levels of AChR-responsive TGF- beta mRNA expressing cells. Thymectomized myasthenia gravis patients s howed higher levels of TGF-beta mRNA expressing cells compared with pa tients not thymectomized. Numbers of cells responding to AChR in MS an d MBP in myasthenia gravis did not differ from numbers found in absenc e of antigen. Patients with other neurological diseases showed infrequ ent and low responses to MBP, PLP, and AChR. Diseases with presumed au toimmune pathogenesis are associated with organ-specific autoantigen-i nduced TGF-beta production, which is increased after thymectomy.