Human T‐cell response to myelin basic protein in multiple sclerosis patients and healthy subjects

Abstract

In order to explore the T-cell repertoire to myelin basic protein (BP) of both multiple sclerosis (MS) patients and healthy subjects (HS), we raised BP reactive T-cell lines from blood mononuclear cells of eight MS patients and five HS. These lines were triggered in vitro by human BP. When analyzing their patterns of recognition of human BP versus heterologous BP, we could observe differences between healthy subjects and MS patients. Whereas T-cell lines from healthy subjects developed a response to heterologous BP, which was in most cases equal or higher than that elicited by human BP, T-cell lines from most MS patients displayed a low response, or no response at all, to one or several of the heterologous BP tested. A low response to bovine BP was only observed in active cases, whereas decreased responses to rat and/or monkey BP were observed both during remission and during active disease. This may indicate that T-cell repertoire to BP in MS patients differs from that of healthy subjects. BP-reactive T-cell clones were obtained by limiting dilution from two healthy subject lines. Their pattern of response to heterologous BP as compared to human BP suggest that T-cells from the same individual can recognize different BP epitopes.

The sad plight of multiple sclerosis research (low on fact, high on fiction): critical data to support it being a neurocristopathy

“…These experiments were repeated, however, and found wanting (Brinkman et al 1982;Burns et al 1983). Further studies failed to show that there were increased numbers of specific sensitised clones of T lymphocytes to myelin antigens in patients with MS (Burns et al 1983;Richert et al 1983;Hafler et al 1985;Tournier-Lasserve et al 1988). Notwithstanding these failures, the protagonists have put forward the idea that the T-receptor gene might be different in T-lymphocyte clones from MS patients as compared to the T-cell receptor gene usage of similar clones in patients without MS.…”

Reactivity to myelin antigens in multiple sclerosis. Peripheral blood lymphocytes respond predominantly to myelin oligodendrocyte glycoprotein.

“…Although a low frequency of MBP-responsive MS patients was unexpected, in view ofthe data ofsome previously published studies (39)(40)(41)(42)(43) and the assumption that MS is associated with the response to MBP, these results are in line with other studies where PBL sensitization to MBP could be detected in some MS patients, but also in patients with other neurological diseases and in healthy controls ( 37,(44)(45)(46)(47)(48)(49)(50). Similarly, our data on PLP reactivity, whereby 2 of 24 MS patients reacted positively to this antigen, are in agreement with some studies but in disagreement with others, as diverging results have been obtained by various groups assessing PLP sensitization in MS.…”

Myelin autoreactivity in multiple sclerosis: recognition of myelin basic protein in the context of HLA-DR2 products by T lymphocytes of multiple-sclerosis patients and healthy donors.

“…The presence of hMBP-reactive T-cell clones within the immune repertoire of healthy donors is not too surprising (26,27), since lethally encephalitogenic MBP-specific T-cell lines can be isolated from the immune system of completely normal Lewis rats, which never spontaneously develop experimental autoimmune encephalomyelitis (EAE)-like disease (28). Hence, the presence of hMBP-reactive T-cell precursors in healthy human beings does not argue per se against a pathogenic potential of these cells in MS.…”