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SUMMARYUsing three-colour flow cytometry, we have measured intracellular IL-2, interferon-gamma (IFN-°) and tumour necrosis factor-alpha (TNF-®) induced in human CD4 + and CD8 + T cells from normal donors and patients with common variable immunodeficiency (CVID). Since a new range of directly FITC-conjugated anti-cytokine antibodies was used, conditions were optimized for the concentration of antibody, for cell permeabilization and fixation, and for the time of exposure to monensin to retain the cytokines within the cell. Kinetics of intracellular cytokine production were measured for up to 20 h in culture with phorbol myristate acetate (PMA) and ionomycin, or with phytohaemagglutinin (PHA). Kinetic studies of activation with PMA and ionomycin show that a higher proportion of normal CD4

Peripheral vascular malformations encompass a wide spectrum of lesions that can present as an incidental finding or produce potentially life-or limb-threatening complications. They can have intra-articular and intraosseous extensions that will result in more diverse symptomology and present greater therapeutic challenges. Developments in classification, imaging and interventional techniques have helped to improve outcome. The onus is now placed on appropriate detailed preliminary imaging, diagnosis and classification to direct management and exclude other more common mimics. Radiologists are thus playing an increasingly important role in the multidisciplinary teams charged with the care of these patients. By fully understanding the imaging characteristics and image-guided procedures available, radiologists will be armed with the tools to meet these responsibilities. This review highlights the recent advances made in imaging and the options available in interventional therapy.Peripheral vascular malformations (PVMs) encompass a wide spectrum of lesions that can present as an incidental finding or produce potentially life-or limb-threatening complications. PVMs are relatively common within the extremities and usually confined to the subcutaneous tissues and muscles. They can have, however, intra-articular and intraosseous extensions that will result in more diverse symptomology and present greater therapeutic challenges. Any misdiagnosis can lead to inappropriate management and treatment.

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We show that LPS-stimulated circulating CD14-positive monocytes from patients with common variable immunodeficiency (CVID) express a higher proportion of intracellular IL-12-positive cells than monocytes from patients with X-linked agammaglobulinemia or normal subjects. We used four-color flow cytometry and measured IL-12 with an Ab to the p40 subunit following stimulation with LPS. The raised IL-12 is associated with an increased frequency of IFN-γ-positive T cells, but not of IFN-γ-positive CD56+ NK cells. These increases in frequency of cytokine-positive cells are due to a decrease in the absolute numbers of circulating monocytes and T cells that are negative for IL-12 and IFN-γ, respectively. The increased frequency of IL-12-positive monocytes appears to be selective because TNF-α was not increased, and is thus unlikely to reflect a general activation. Chronic infection is also unlikely to explain our data since cells from X-linked agammaglobulinemia patients with a similar Ig deficiency do not show these changes. Our data suggest a fundamental abnormality in the IL-12/IFN-γ circuit in CVID, with up-regulation of IL-12 being the “primary” factor. This imbalance is likely to skew the immune response away from Ab production and also explains the failure of CVID T cells to make Ag-specific memory cells and the chronic inflammatory and granulomatous complications that are a feature of CVID. This disease appears to be a rare example of a polarized Th1-type response and may in part be due to a genetic defect in the control of IL-12 production.

SUMMARYSeveral T cell defects have been described in the antibody deficiency disease, CVID, but there have been few data on the generation of responses of specific T cell populations to primary neoantigens. We have now used immunization with the neoantigens, keyhole limpet haemocyanin (KLH) and DNP-Ficoll, to evaluate immune responses in CVID patients and normal donors. B and T cell responses were examined 2 and 4 weeks post-immunization. Sera were examined for IgM and IgG anti-KLH responses by ELISA and for anti-DNP-Ficoll activity by haemagglutination. The frequency of KLH-responsive T cells was measured by DNA synthesis in a limiting dilution culture system. Low density cells enriched for dendritic cells were pulsed with KLH and cultured with different numbers of autologous T cells. T cells from normal donors and from patients showed a low frequency of antigen-specific precursor T cells (Յ1:200 000). After KLH immunization the frequency increased in normal donors (1:60 000 and 1:30 000 at 2 and 4 weeks, respectively), while in CVID patients it did not change from the preimmunization level. The defect may extend to a dysfunction of antigen-specific cells, rather than being solely due to the reduced numbers of cells, since mean responses of 'positive' wells were also reduced. The serum-specific antibody response paralleled the T cell data, in that all normal donors but none of the CVID patients generated IgG KLH-specific antibodies. CVID patients did produce IgM antibodies against the T-independent DNP-Ficoll, but at a lower level than normal controls. These data show that both T and B cells from CVID patients have defective responses to specific antigen, implicating both lineages in the antibody deficiency.

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