Multiple Sclerosis as a Disease of Immune Regulation

Abstract

Conclusions

Most available evidence suggests that infection with enveloped viruses of the myxo-, paramyxo-, herpes-, and poxvirus families may occasionally induce immunization to neural antigens, myelin antigens in particular, and a consequent encephalomyelitis localized to the white matter. In individuals with a genetically determined abnormality of immune regulation, this process may not be suppressed and may give rise to the recurrent or long-lasting periods of new lesion formation which we call multiple sclerosis. Exacerbations may be provoked by further virus infections or by childbirth. The responsible white matter antigen(s) have not been firmly identified and the immunoregu-latory abnormality is unknown. The character of the lesions appears to be determined by multiple simultaneous immune responses to different antigens and multiple superimposed immunopathologic effects.

Much of what is presented in the present review may require revision as the further application of monoclonal antibody techniques (127) and the new techniques of cloning, fusing, or otherwise immortalizing T cells (128) reveals previously unsuspected neural or viral antigens in white matter and effector molecules and/or cells reactive with these antigens. Thus, in mouse experiments Reovirus strains infecting the pituitary and pancreas have been shown to produce intense immunization to a variety of autoantigens in these organs (M. Haspel, in (4)). The range of actual responses was uncovered only by carrying out fusions with infected animals' spleen cells and studying the hybrids thus obtained. Similarly continuous “monoclonal” lines of T cells specific for a single myelin antigen are being studied for their ability to produce EAE (129). At least seven laboratories in the United States and several abroad are hybridizing B cells and cloning the two principal classes of T cells, helper/inducer and cytotoxic/suppressor, from MS patients' blood and CSF, and the clones are being examined for reactivity with neural and viral antigens.