Immune regulation in adjuvant disease and other arthritis models: relevance to pathogenesis of chronic arthritis.

Experimental models of arthritis and their human counterparts fall into three distinct classes: (a) responses of T cells to disseminated microbial antigens (Ags) as such; (b) responses of T cells to cartilage autoAgs; and (c) responses of T cells to major histocompatibility complex (HLA-B27, DRB1) or other membrane components (LFA-1) expressed on bone marrow-derived cells. The primary immune response is driven, in naturally occurring disease, by microbial infection, e.g.

Thymus and tolerance. Is regulation the major function of the thymus?

This paper will serve as a contribution to the current reassessment of the relative roles of clonal selection and regulation in specific immunologic tolerance. We review basic studies in the Waksman laboratory that first established the importance of the thymus in tolerance and the possible contribution of regulatory cells generated in the thymus to self-tolerance. Experimental evidence is presented to suggest that there exists a wide range of immunoregulatory mechanisms, many of which deserve more intensive investigation in relation to the tolerance question.

Demyelinating disease: evolution of a paradigm.

Multiple sclerosis was at one time viewed as a spiritual (God-given) disorder; only much later was it recognized as a scarring process. With advancing scientific knowledge, it was seen as a primarily demyelinating disease, later as thromboembolic in origin, and finally as inflammatory and destructive, probably an immunologic response to exogenous (infectious) agents or to one or more autoantigens. The pathogenesis of lesions was first ascribed to antibody, later to inflammatory cells, acting via a panoply of mediators, such as cytokines, adhesion molecules, chemokines, and complement components.