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Biomedical subjects

S C Knight

Publications and source records attributed to S C Knight.

At least 163 records · Page 9Linked to original sources
PubMed1976

The effect of intensive immunosuppression on the in vitro activity of lymphocytes from multiple sclerosis patients.

During a small clinical trial of intensive immunosuppression in multipel sclerosis (MS, 14 patients) the changes of in vitro lymphocyte responses to mitogens were followed. A variable depression of the normal responses to phytohaemagglutinin (PHA), Concanavalin A (Con A) and pokeweed mitogen (PWM) was seen in the patinets during the inital week of treatment with prednisone (150 mg/day tapered to 20 mg/day by day 7), and azathiprine (3 mg/kg daily). They were further depressed during antilymphocyte globulin therapy (ALG 500 mg/day on weekdays, weeks 2-5 of treatment). These responses returned rapidly to the lower normal range after the three weeks of ALG despite the continued prednisone and azathipprine therapy. A complex effect of immunosuppression on lymphocyte subpopulations was suggested by three findings. Firstly, in contrast with the reduction in response to plant mitogens no lowering of the response to allogeneic lymphoid cell line cells (LCL) was seen during the first week of treatment. Secondly, some patinets, particularly those expressing the HLA-7 antigen, had a low pre-treatment response to LCL which showed an improvement during treatment and which was maintained through the first week of ALG treatment. Thirdly, single inviduals sometimes showed different degrees of suppression of different responses during and after ALG treatment. Occasionally, responses showed some recovery even during the ALG treatment, suggesting that higher ALG doses were required in these patients. The results suggest that the action of immunosuppressive drugs on lymphocyte activity differs between individuals due to the heterogeneity of the lymphocyte subpopulations present.

Antilymphocyte Serum↗
PubMed1975

Intensive immunosuppression in patients with disseminated sclerosis. III. Lymphocyte response in vitro.

Lymphocytes from fifteen multiple sclerosis patients gave responses to phytohaemagglutinin (PHA), conconavalin A (con A) and pokeweed mitogen (PWM) which were in the normal range. However, the responses of lymphocytes to stimulation by an allogeneic lymphoid cell line (LCL) were significantly lower in HLA-7-positive than in HLA-7-negative patients (a distinction not found in control groups). Depression of con A, PHA and PWM responses were observed during intensive immunosuppression. Responses to LCL were unaltered or increased during initial azathioprine and prednisone treatment. The depression of this response following antilymphocyte globulin (ALG) treatment was delayed in the HLA-7-positive patients. One week after the end of ALG treatment, most PHA, con A and PWM responses had returned to low normal values. Reduction of azathioprine and prednisone treatment at the end of 1 year resulted in a sharp rise in PHA and con A responses in some patients. Relapses in patients were frequently associated with low responses to LCL cells.

Antilymphocyte Serum↗
PubMedDate not supplied

Dendritic cells in contact sensitivity.

Bone-marrow-derived DC, passing through the skin or residing there as LC, acquire antigen following epicutaneous exposure to contact sensitizer. They move as veiled cells in the afferent lymphatics and migrate to draining lymph nodes, where they become interdigitating cells of the paracortex. Here they initiate T-cell responses; the cytotoxic T cells and antibody formation which develop may be able to target on DC as well as other antigen-bearing cells, so producing feed-back mechanisms to switch off immune responses. Additional features include a systemic effect which leads to movement of DC without antigen into lymph nodes. What are the signals leading to this movement and what is its significance? There is evidence for synergy between directly haptenated DC and DC not directly acquiring antigen. How does this occur and how important is this effect in ensuring the potency of DC in presenting contact sensitizer to T cells? What is the importance of antigen processing by LC? Finally, dendriform cells which may be of T-cell origin are also present in the skin. What is their role in modulating the development of contact sensitivity?

Animals↗
PubMedDate not supplied

Effect of HIV on antigen presentation by dendritic cells and macrophages.

The antigen-presenting function of dendritic cells (DC) and macrophages (MO) following infection with HIV in vitro was examined. Using non-infected cells, DC, but not MO, stimulated primary proliferative responses in allogeneic lymphocytes in the mixed leukocyte reaction. Both DC and MO stimulated secondary responses to influenza virus and to tetanus toxoid in autologous T lymphocytes. After exposure of DC and MO to HIV1 in vitro for 2 days, 27% of DC but less than 1% MO became infected as assessed by in situ hybridization. DC were blocked in their capacity to stimulate responses to alloantigens or to the recall antigens. By contrast, MO retained the ability to stimulate responses to the recall antigens. Similar effects during in vivo infection would allow activated T-cell clones to respond to antigens presented by MO early in infection. However, any loss of activated T cells might prove cumulative and damaging in the absence of an effective DC recruitment mechanism for resting T cells.

Antigen-Presenting Cells↗
PubMedDate not supplied

The effect of AZT on dendritic cell number and provirus load in the peripheral blood of AIDS patients: a preliminary study.

In this pilot study, the numbers of dendritic cells (DC) in peripheral blood of AIDS patients and the level of infection with HIV1 were determined before and after AZT treatment. Mononuclear cells were cultured overnight and DC were identified by their lack of labelling with antibodies specific for T, B and natural killer (NK) cells and monocytes and by their high level of staining with antibodies for MHC class II molecules. Although the numbers of DC identified by this method were lower than those identified morphologically in earlier studies (Macatonia et al., 1990), the numbers in three untreated AIDS patients were below the range seen in normals. There was also a marked rise in DC number in patients given AZT therapy. In two patients, there was a significant provirus load in the DCs which was decreased two to three weeks after the commencement of AZT therapy. The studies suggest that DC numbers and their infection levels may be markers of disease in HIV infection.

Acquired Immunodeficiency Syndrome↗