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Based on methods used for the in vitro induction of antigen-specific suppressor cells in the mouse, we have cultured Ficoll-Isopaque-separated human blood cells with high dose of antigen (100 μg/ml) in Marbrook culture vessels for 4 days. The resulting cells, when further recultured for 24 hr with a low dose of antigen (1 μg/ml), released into the supernatant material, termed 'suppressor factor', which inhibited, in an antigen-specific manner, the antibody response of mouse spleen cells in culture. The suppressor factor was analysed using immunoabsorbents, and was bound to and eluted from specific antigen, concanavalin A and lentil lectin, anti-human la antibodies, and anti-mouse suppressor factor antibodies, but was not bound to antibodies against human IgG. [ABSTRACT FROM AUTHOR]

Mononuclear cells (10-20 × 106) obtained from human peripheral blood by a standard Ficoll-Hypaque technique were suspended in RPMI 1640 media at 4°C containing 10% foetal calf serum and 7.5% dimethyl sulphoxide (DMSO). Two- millilitre aliquots were cooled at - 1°C/min in a Cryoson BV-4 programmed freezing system to - 30°C, then - 5°C/mm to - 80°C and stored in liquid nitrogen vapor. On the day of testing, cell suspensions were thawed rapidly in a 37°C water bath. DMSO was diluted slowly out of the sample and cells resuspended in fresh RPM [1640. it was found that frozen stored human lymphocytes (FSHL) demonstrated all the characteristics of fresh unfrozen cells. These included their ability to form spontaneous rosettes with sheep erythrocytes (`E' rosettes) and sheep erythrocyte-antibody--complement rosettes (`EAC' rosettes). The presence of surface immunoglobulins and Fc receptors were shown by membrane immunofluorescence to be comparable. in addition, the results show that FSHL respond to mitogens, specific antigens; act as both stimulators and responders in the mixed lymphocyte culture reaction; and exhibit cell-mediated lymphocytotoxicity following in vitro sensitization, or against antibody-coated target cells. [ABSTRACT FROM AUTHOR]

Influenza virus immune human T-lymphocyte clones maintained in continuous culture in TCGF were analysed for helper activity and interleukin-2 (IL-2) production. The clones that functioned as helper cells in the production of specific antibody failed to release detectable amounts of IL-2. Conversely, the T cells that produced IL-2 were unable to provide either specific or non-specific helper function. These findings indicated the IL-2 is not an essential component for helper activity. However, phenotypic analysis revealed that both the functional subsets of T-cell clones expressed the helper phenotype in that they were T4+, T3+ and T11+ Nevertheless analysis with other antibodies revealed differences in that the IL-2 releasing clone showed greater staining with the anti-T-cell subset antibodies 9.3 and Leu 8, confirming that there is phenotype as well as functional heterogeneity within the helper inducer T-cell population. [ABSTRACT FROM AUTHOR]

Juvenile chronic arthritis (JCA) is the commonest chronic rheumatic disorder of childhood. Although conventional therapy of JCA continues to improve, many patients experience long-term ill health as a result of their disease or treatment. In adult rheumatoid arthritis (RA), similar concerns have led to the development of therapies designed to interfere in key disease processes. One such therapy is cA2, a chimeric neutralizing monoclonal antibody to the inflammatory cytokine, tumour necrosis factor-alpha (TNF-alpha). The administration of cA2 in adult RA has led to impressive short-term suppression of disease, with a good safety profile. Here, we report the first use of cA2 in childhood arthritis, choosing a patient with severe systemic-onset JCA, resistant to conventional therapies. The patient received two i.v. infusions of cA2, each at a dose of 10 mg/kg, separated by 1 week. The treatment was well tolerated and induced rapid control of fever, anorexia and serositis, together with downregulation of interleukin (IL)-6, soluble TNF receptors (sTNFR) and IL-1ra, and the acute-phase proteins C-reactive protein (CRP) and serum amyloid A (SAA). In contrast, we saw no significant improvement in joint pain or tenderness. Our findings suggest that TNF-alpha is a mediator of fever and other systemic aspects of disease in systemic JCA. TNF-alpha blockade as a treatment modality in JCA deserves further study. [ABSTRACT FROM PUBLISHER]

The generation of human antigen-specific helper cells from unprimed peripheral blood lymphoid cells in tissue culture requires the presence of the appropriate number of blood monocytes. The role of the H LA complex in this cell interaction was investigated, by using HLA-typed donors, and it was found that the monocytes had to share at least one HLA-DR specificity with the T cell donor. These experiments suggested that the genes controlling the macrophage T cell interaction are closely associated or in linkage disequilibrium with the HLA-DR region. [ABSTRACT FROM AUTHOR]