Inhibition of Experimental Allergic Encephalomyelitis with an Antibody that Recognizes a Novel Antigen Expressed on Lymphocytes, Endothelial Cells, and Microglia

Abstract

SUMMARY:Experimental allergic encephalomyelitis (EAE) is a frequently employed animal model of the human disease multiple sclerosis. EAE can be induced by adoptive transfer of CD4 ϩ T cells that are specific for central nervous system (CNS) antigens, typically myelin proteins. Although the pathogenic mechanism or mechanisms responsible for the clinical signs and histological changes in EAE and multiple sclerosis are not fully defined, the entry of T lymphocytes and antigen recognition within the CNS are required. The present study describes the participation of a novel cell surface molecule with properties suggesting a role in cell-cell adhesion or co-stimulation, or both, in the development of EAE in the rat. The molecule is defined by the unique monoclonal antibody (mAb) TLD-4A2. The TLD-4A2 antigen is present on resting and activated T lymphocytes, activated CNS endothelial cells, and microglia. The antigen is normally distributed in many tissues including lymph node, thymus, and spleen, as well as in the inflamed CNS. Both its pattern of tissue distribution and immunoprecipitation and immunoblotting studies suggest that the TLD-4A2 antigen is a novel molecule. Treatment of rats with the purified 4A2 mAb resulted in the inhibition of the clinical signs of EAE and also decreased the number T cells and macrophages accumulating in the CNS parenchyma. TLD-4A2 antibody did not seem to directly interfere with T cell viability in vivo, as demonstrated by the ability to recover and stimulate CD4 ϩ encephalitogenic T cells from cervical lymph nodes of 4A2-treated animals. In vitro, the antibody partially blocked T cell proliferation assays. These data suggest that the TLD-4A2 mAb recognizes a novel molecule expressed on lymphocytes, endothelial cells, and macrophages that may play a role in hematogenous cell traffic and the initiation of CNS inflammation. (Lab Invest 2000, 80:313-326).

Angiogenesis is present in experimental autoimmune encephalomyelitis and pro-angiogenic factors are increased in multiple sclerosis lesions

“…These results were similar to those found for collagen IV (Table 3). Similar to previous results we found that CD31 staining was present in a more diffuse pattern on endothelium in the inflamed CNS on some blood vessels (Figure 2) [28] and even disappeared on other blood vessels as noted by Tham and colleagues [29]. …”

Pathogenesis of some neurological immune ultrastructural and morphometrical observations on rat thymus

“…Studies on the role of thymus in auto-immunity start around the years 1968-1969 10,11 . Recently it re-entered into fashion [12][13][14][15] owing to the discovery of new antibodies which recognize particular antigens implied in these neurological diseases. In order to clarify the possible role of thymus microenvironment in the pathogenesis of EAE, an ultra-structural analysis of thymus architecture in rats experimentally induced for EAE was made.…”

Antisecretory factor expression is regulated by inflammatory mediators and influences the severity of experimental autoimmune encephalomyelitis

“…Among the many functions of these cells is their ability to present antigen to infiltrating T cells and thus control the initiation of an immunological response in situ [2]. Although a number of molecules known to be involved in T cell-antigen presenting cell (APC) interactions have been demonstrated to be expressed by PVCs and microglia, we have undertaken studies to identify novel molecules expressed by these cells that participate in these interactions [3,4]. The TLD antibodies are a panel of monoclonal antibodies generated by immunization of mice with living rat microglial cells [5].…”