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Studies on the in vivo effects of interferon-beta (IFNbeta) therapy on autoreactive T cells have never been carried out in multiple sclerosis (MS). We investigated the T cell response to myelin basic protein (MBP), before and after IFN-beta therapy, raising MBP-specific T cell lines (TCL) from the peripheral blood of six MS patients with a satisfactory response to the treatment. IFNbeta did not affect the relative frequency and epitope specificity of the TCL. After IFNbeta therapy, the production of interleukin-4 was decreased in MBP-stimulated TCL while the secretion of interferon-gamma was increased in unstimulated TCL. Interleukin-10 and tumor necrosis factor-alpha did not show significant variations. This finding supports recent suggestions about the complexity of the T helper 1/T helper 2 paradigm in MS and other organ-specific autoimmune diseases. In fact, the beneficial effects of IFNbeta do not exclude an immunostimulatory action that may involve potentially autoreactive T cells. This has implications for future treatment options, including combination therapies.

This report discusses some of the paper presented during the 2nd T Cell Autoimmunity in MS Workshop held in Perugia on November 26–28, 1992. The ‘trait d'union’ of the meeting was the awareness that recent studies have failed to uncover clear-cut differences in T cell reactivity to autoantigens between patients with multiple sclerosis and healthy individuals. Hence, new strategies have been proposed to try to distinguish between “pathological’ autoimmunity in patients and ‘natural’ autoimmunity i healthy individuals. Futhermore, the studies have been extended to new potential autoantigens (myelin constituents other than myelin basic protein, superantigens, heat shock proteins) a new susceptibility genes such as those coding for transport-associated proteins (Tap-1 and Tap-2).

Increasing evidences show a global immune disregulation in multiple sclerosis (MS). The possible involvement of myelin and non-myelin (auto-)antigens in the autoaggressive process as well as the disregulation of both adaptive and innate immunity challenge the concept of specific immunotherapy. T cells at the boundary between innate and adaptive immunity, whose immunoregulatory role is becoming increasingly clear, have recently been shown to bear relevance for MS pathogenesis. Global immune interventions (and type I interferons may be considered as such) aimed at interfering with both innate and acquired immune responses seem to be a most promising therapeutic option in MS.

In multiple sclerosis (MS), the signs of inflammation that can be detected in the central nervous system are not mirrored by unequivocal markers of activation of the immune system in the periphery. We performed a serial monitoring of serum amyloid A protein (SAA), a major acute phase reactant, in peripheral blood of patients with relapsing–remitting MS over a 3-month period. Patients were monitored in parallel with gadolinium-enhanced magnetic resonance imaging (Gd-MRI) of the brain. The results show that signs of ongoing peripheral inflammation, reflected by elevations of SAA levels, can be detected in MS patients.

The MHC region on 6p harbors at least one susceptibility gene for multiple sclerosis (MS). Within this region, HLA-DM loci are of interest being involved in class II antigen processing. We investigated the association of HLA-DM polymorphisms with MS. Sixty-three patients with MS and 46 healthy controls from continental Italy were typed for HLA-DM polymorphisms and HLA-DRB1 alleles. Besides, among the donors characterized for the DM polymorphisms, we considered 6 MS patients previously studied for the fine specificity of their MBP-specific T lymphocyte lines (TLL). The frequencies of allelic variants at the DMA and DMB loci were similar between MS patients and controls, even when HLA-DRB1*1501 positive and negative donors were analyzed separately. Patients with predominant responses to different MBP epitopes did not differ for their HLA-DM haplotype while patients with predominant responses to the same MBP epitope could present different HLA-DM haplotypes. HLA-DM polymorphisms do not associate with MS and may not affect specific patterns of T cell responses to MBP.