The inflammatory reaction of paraneoplastic ganglionitis and encephalitis: an immunohistochemical study.

To elucidate the cellular mechanisms of tissue injury in paraneoplastic states, tissues from two patients with small cell carcinoma of the lung and paraneoplastic neurological syndromes were studied. One patient had encephalitis with ganglionitis, and the other ganglionitis. Immunocytochemistry on brain and ganglia was performed using monoclonal and polyclonal antibodies. The majority of the inflammatory cells in brain and ganglia were T-cells, of both helper and cytotoxic subtypes. There were more macrophages in the inflammatory infiltrate of ganglia than in the brain of encephalitis. Major histocompatibility complex class I and II antigen expression was greater in the mononuclear cells in brain than in ganglia. There was no evidence of complement deposition and little evidence for antibody synthesizing cells. Our findings suggest a T-cell-mediated immune attack in paraneoplastic ganglionitis and encephalitis, with a greater role for macrophages in ganglionitis.

Macrophages, microglial cells, and HLA-DR antigens in fetal and infant brain.

Immunohistochemical reactions for macrophages, microglia, and HLA-DR antigens were tested on frozen sections of necropsy brain tissue from 20 fetuses and infants ranging in age from 18 weeks' gestation to 8 months post term. No primary central nervous system disease was present but there were four cases of sudden infant death syndrome (SIDS). Macrophages were detected in all the samples studied and were located in the germinal matrix zone, in perivascular spaces throughout the brain, and in the leptomeninges and subependymal layer. Well differentiated microglia were present in all cases examined after 35 weeks' gestation and less well ramified forms were seen at earlier stages of gestation. HLA-DR antigens were detected on a small number of macrophages, chiefly in a perivascular location, in all but three cases. The fewest reactive cells and the weakest reactions occurred in the youngest fetuses. One case of SIDS showed increased foci of microglia in perivascular white matter: this case and one other case of SIDS were the only cases with well ramified microglia that expressed HLA-DR antigens. These findings may be relevant to an understanding of local immune responses in fetal brain infections, including human immunodeficiency virus infection.

Macrophages, lymphocytes and major histocompatibility complex (HLA) class II antigens in adult human sensory and sympathetic ganglia.

We report an immunocytochemical study of sensory and autonomic ganglia from ten adult human subjects aged 18-83 years without peripheral nerve disease using monoclonal antibodies to macrophages, lymphocytes and human leukocyte (HLA) class II antigens. All ganglia and their associated nerve roots were found to contain a population of resident macrophages which accounted for 5-20% of the cells present. These macrophages and, in addition, many Schwann cells and satellite cells, gave reactions for HLA class II antigens in all cases. Very low numbers of CD3 and CD8 lymphocytes were also regularly detectable in sensory and autonomic ganglia. The resident macrophages may have important immunological and trophic functions. Their possible role in the development of immune-mediated peripheral nerve disease deserves further study.

Immunocytochemical characterization of the macrophage and lymphocyte infiltrate in the brain in six cases of human encephalitis of varied aetiology.

Monoclonal antibodies that react with various macrophage and lymphocyte sub-populations have been applied to acetone-fixed cryostat sections of brains from six cases of human meningo-encephalitis (two cases of subacute sclerosing panencephalitis, two cases of allergic encephalitis, one case of suspected entero-virus meningo-encephalitis and one case of meningo-encephalitis of undetermined origin). The patterns of inflammatory cell response that these antibodies reveal is described and discussed in comparison with published descriptions of the corresponding cell types found in the brain in Japanese encephalitis, herpes simplex encephalitis and multiple sclerosis. In general, in the acute phases of inflammatory central nervous system diseases, T lymphocytes and macrophages predominate in the parenchyma, while the early phases of a B cell response take place in perivascular spaces.

Macrophage populations associated with multiple sclerosis plaques.

The macrophage population within and outside plaques from eight cases of multiple sclerosis (MS) (two clinically acute, four chronic progressive and two chronic non-progressive) has been examined in fresh frozen sections with a panel of monoclonal antibodies of macrophage, monocyte and MHC class II specificity. The majority of cells in active, hypercellular plaques, and at active borders, reacted with macrophage- and class II MHC-specific antibodies, and such cells extended beyond the border between demyelinated and myelinated parenchyma. In inactive plaques such cells that reacted with macrophage-specific antibodies were sparse and reacted only inconstantly with class II MHC-specific antibodies. Macrophage heterogeneity was evident in as much as one macrophage antibody, RFD7, reacted only with perivascular and not parenchymal macrophages in most plaques, but reacted with a variable proportion of parenchymal macrophages in active plaques. It is suggested that the RFD7 antibody may identify a sub-population of acute plaques, and that its use may clarify interpretation of findings related to other inflammatory cell populations by providing greater precision of classification of active plaques.