Lymphocyte transformation in the presence of myelin basic protein in multiple sclerosis and control subjects

Abstract

The transformation of lymphocytes in vitro in the presence of human myelin basic protein has been investigated in normal people, patients with multiple sclerosis (MS) and controls with other neurological diseases. There was little or no response at low concentrations (1-10 pg/ml) but significant transformation at higher concentrations (100-1000 pg/ml) in all three groups. There was no significant difference among the groups as a whole, but those MS patients who had had disease for more than 10 years did show greater responses than normal subjects (P<0.05). Increased responses could not be correlated with any other aspect of disease activity: in particular they were not increased in patients with acute relapses. The use of autologous serum instead of homologous AB Rhesus positive serum did not significantly alter lymphocyte responsiveness. The absence of any response in the presence of purified calf thymus histone suggests that the response to myelin basic protein indicates a low level of lymphocyte sensitization to this antigen even in normal subjects. The present evidence does not support a primary pathogenetic role for such a reaction in MS. The increased response in patients with a long duration of disease might merely be an effect of white matter damage or might represent an amplification of the normal immune response contributing to myelin breakdown and leading to the emergence of the progressive stage of the disease. The study of lymphocyte responsiveness over a wide range of concentrations of myelin basic protein is considered to resolve some of the controversy surrounding this subject in the literature.Experimental allergic encephalomyelitis is still proposed as a model of MS because it is histologically similar to the human disease and chronic forms can be produced (Snyder et al. 1975). The experimental disease is known to require a cell-mediated immune reaction against myelin basic protein which can be demonstrated by positive intradermal skin tests in vivo or by lymphocyte transformation or macrophage inhibitory factor production in vitro. If experimental allergic encephalomyelitis is relevant to MS, clinical immunological evidence of sensitization to myelin basic protein should be obtainable 0001-6314/79/080065-12 $0.2.50/0 @ 1979 Munksgaard, Copenhagen 5' gen-binding lymphocytes in normal man and guinea pig to human encephalitogenic protein.

Multiple sclerosis - lymphocyte transformation with multiple sclerosis and normal brain myelin basic protein and subcellular fractions

“…This study has confirmed our previous finding that lymphocytes from patients with acute relapses of MS do not show enhanced transformation in the presence of normal human myelin basic protein ( Hughes et al 1979). We then reviewed the conflicting evidence available in the literature.…”

“…The transformation of the lymphocytes from this group was sufficiently greater than that of the lymphocytes from normal controls in the presence of MS myelin basic protein and MS synaptosomes to achieve significance at the 5 % level (Figs. We previously found that patients with chronic MS had increased lymphocyte transformation in the presence of normal myelin basic protein (Hughes et al 1979). The significance of this result in the present study can be seen to be due to two of the six patients (Fig.…”

“…Myelin basic protein was prepared from separate portions of the same brains by extraction of whole white matter with hydrochloric acid (Hughes et al 1979). The normal brain was dissected within 10 h of death and stored at -2OOC for 3 months and the MS brain was obtained after 2 days and dissected after similar storage for 5 months.…”

“…Conditions were as in our previous experiment (Hughes et al 1979) with two minor alterations: 20 mM Hepes buffer was added to the bicarbonate buffered tissue culture medium and an increased amount, 0.8 pCi, of 3Hthymidine was added to each well 24 h before harvesting. Conditions were as in our previous experiment (Hughes et al 1979) with two minor alterations: 20 mM Hepes buffer was added to the bicarbonate buffered tissue culture medium and an increased amount, 0.8 pCi, of 3Hthymidine was added to each well 24 h before harvesting.…”

“…In MS most studies of immunity to brain antigens have used normal brain extracts and given negative results (for review see Hughes et al 1979), but MS brain might have antigenically important biochemical alterations, due either to an inherited biochemical defect or to a persistent viral infection. Therefore tests for immunity would be more appropriately applied to extracts of MS brain.…”