ORGAN-SPECIFIC AUTOANTIGENS INDUCE INTERFERON-GAMMA AND INTERLEUKIN-4MESSENGER-RNA EXPRESSION IN MONONUCLEAR-CELLS IN MULTIPLE-SCLEROSIS AND MYASTHENIA-GRAVIS

T cells recognizing the myelin components myelin basic protein (MBP) a nd proteolipid protein (PLP) are increased in multiple sclerosis (MS), and there are elevated numbers of T cells recognizing the nicotinic a cetylcholine receptor (AChR) in myasthenia gravis (MG). However, the c ytokine repertoires in these diseases are largely unknown. We adopted in situ hybridization with radiolabeled complementary DNA oligonucleot ide probes to enumerate mononuclear cells that expressed the T-helper type 1 (Th1) cell-related interferon-gamma (IFN-gamma) and Th2-associa te interleukin-4 (IL-4) aRer short-term culture in the presence of aut oantigen. High numbers of IFN-gamma and IL-4 mRNA-expressing cells in response to MBP and PLP were detected in patients with untreated MS, a nd to AChR in MG. The levels of TFN-gamma and IL-4 mRNA-positive cells in MS after culture in the presence of AChR, and in MG after culture in the presence of MBP or PLP, did not differ from those detected afte r culture without antigen. The CSF of MS patients contained four- to e ightfold more myelin protein-reactive IFN-gamma and IL-4 expressing ce lls. The findings imply that MS and MG are associated with mixed Th1- and Th2-like cell responses directed to organ-specific target antigens .