ANTIGEN UPTAKE BY SPECIFICALLY REACTIVE CELLS IN EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS *

Recent investigations of the immunologic reactions which occur in experimental allergic encephalomyelitis (EAE) have supplied evidence for the development of cellular or delayed hypersensitivity in this autoimmune disease. Delayed skin reactions to central nerve tissue preparations have been reported'-' in rabbits and guinea pigs with allergic encephalomyelitis; skin responses to homologous nerve tissue correlate fairly well with the severity of the disease process. Histologic studies of the perivascular lesions which occur throughout the central nervous system indicate that they are comparable to the histologic changes in other delayed reactions. Perivenous infiltration of mononuclear cells with prominent perivascular cuffing and invasion of the parenchyma is commonly observed. Radioautographic studies5 in the rat using tritium-labeled thymidine injected a day or more before lesion formation have demonstrated that the cells in the perivascular infiltrates are hematogenous in origin and may be characterized as medium or large lymphocytes, many of which evolve to histiocytes during active proliferation in the lesion. In severe lesions there may also be invasion by polymorphonuclear leukocytes. Cells of the plasmocyte series appear shortly and the presence of plasma cells containing detectable gamma globulin has been suggested to correlate well with severe disease. Species vary in the prominence of demyelination which appears to relate anatomically to the cellular infiltratione6 The most prominent evidence for the role of cellular hypersensitivity in the pathogenesis of this allergic disease includes passive transfer with lymph-node-cell preparations. However, successful transfer studies, unlike the case in delayed hypersensitivity to tuberculin, have been generally limited to immunologically tolerant recipient animals. Passive-cell transfers have been accomplished between inbred guinea pigs' and inbred rats,* with rat recipients prepared by neonatal injection of donor spleen cellsg and with irradiated rabbit recipients.1° In addition, in vitro studies of the effect of lymph-node cells from sensitized rats on tissue culture monolayers of puppy brain demonstrated the phenomenon of contactual agglutination. " In this instance the tissue culture lacked myelinated constituents which contain the inducing antigen in EAE. This reaction may not be similar in nature to tuberculin-type hypersensitivity or tissue cell rejection** since normal lymphnode cells, after incubation with sera from sensitive animals acquired the capacity to agglutinate the cultured cells. Lymphocytes have generally been implicated as the specific cell involved in tuberculin reactivity, the classic example of delayed hypersensitivity. It was early demonstrated that cutaneous tuberculin reactivity could be passively transferred by peritoneal exudate cells containing lymphocyte^. '^ A more direct relationship was established when cells from thoracic duct lymph of tuberculin-positive rabbits and guinea pigs was successfully used for transfer. '* In contrast guinea pig peritoneal exudates almost exclusively composed of granulocytes do not transfer this reactivit~. '~