Premium
Organ‐specific autoantigens induce transforming growth factor‐β mRNA expression in mononuclear cells in multiple sclerosis and myasthenia gravis
Author(s) -
Link Joanne,
Fredrikson Sten,
Söderström Mats,
Olsson Tomas,
Höjeberg Bo,
Ljungdahl Åke,
Link Hans
Publication year - 1994
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.410350211
Subject(s) - myasthenia gravis , immunology , myelin proteolipid protein , peripheral blood mononuclear cell , myelin basic protein , thymectomy , autoimmune disease , multiple sclerosis , proteolipid protein 1 , cytokine , medicine , transforming growth factor , biology , myelin , antibody , central nervous system , in vitro , biochemistry
Multiple sclerosis (MS) is characterized by patchy accumulations of inflammatory cells combined with demyelination. There are mononuclear cells in blood and cerebrospinal fluid of patients with MS that produce interferon‐γ and interleukin‐4 in response to myelin basic protein (MBP) and proteolipid protein (PLP). Here we describe autoantigen‐induced production of transforming growth factor‐β (TGF‐β). This multifunctional cytokine has inhibitory effects on the growth, differentiation, and effector functions of activated T cells. Blood and cerebrospinal 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‐β mRNA expression. Patients with MS had higher numbers of MBP‐ and PLP‐responsive TGF‐β mRNA expressing cells in blood compared with control patients with other neurological diseases or myasthenia gravis and a five‐ and threefold further increment in their cerebrospinal fluid. In blood of patients with myasthenia gravis, where the acetylcholine receptor (AChR) is a target for autoaggressive immunity, there were increased levels of AChR‐responsive TGF‐β mRNA expressing cells. Thymectomized myasthenia gravis patients showed higher levels of TGF‐β mRNA expressing cells compared with patients not thymectomized. Numbers of cells responding to AChR in MS and MBP in myasthenia gravis did not differ from numbers found in absence of antigen. Patients with other neurological diseases showed infrequent and low responses to MBP, PLP, and AChR. Diseases with presumed autoimmune pathogenesis are associated with organ‐specific autoantigen‐induced TGF‐β production, which is increased after thymectomy.