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We have established a large panel of T-cell clones (TCCs) specific for Dermatophagoides pteronyssinus and Loliumperenne group I grass pollen allergens (total, 61) and for tetanus toxoid and protein purified derivative bacterial antigens (total, 38) from the peripheral blood of two atopic Individuals and then analyzed their ability to produce interleukin 4 (IL-4), IL-5, and interferon y (IFN-y). Upon stimulation with phorbol 12-myristate 13-acetate plus anti-CD3 antibody, the great majority of TCCs specific for bacterial components was able to produce both IL-4 and IFN-y, whereas most D. pteronyssinus-and L. perenne group I-specific TCCs produced IL-4, but no, or limited, IFN-y. Moreover, the mean amounts of IL-4 and IFN-y released by allergen-specific TCCs were significantly higher and lower, respectively, than the mean amounts produced by TCCs specific for bacterial components. Under the same experimental conditions, virtually all allergen-specific TCCs, but only one-third of tested TCCs specific for bacterial components, expressed IL-5 RNA and secreted IL-5 in their supernatants. Eighteen TCCs (nine specific for allergens and nine specific for bacterial compo-

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Infection of CD4+ T cells by human immune deficiency virus-1 (HIV-1) causes severe dysfunction of cellular immunity, but paradoxically results in intense polyclonal activation of B cells, possibly accounting for both hypergammaglobulinaemia and frequent development of B-cell malignancies seen in HIV-infected patients. We have reported that human CD4+ T-cell clones infected with HIV in vitro markedly stimulate immunoglobulin synthesis by B cells through a non-cognate, contact-dependent mechanism. We show here that HIV-infected T-cell clones do not express the CD40 ligand (CD40L), a molecule critical for non-cognate B-cell activation, but a small proportion of them do express membrane tumour-necrosis factor (TNF)-alpha. The ability of HIV-infected T-cell clones to induce polyclonal B-cell activation appears to be restricted to TNF-alpha-positive T blasts and is inhibited by antibodies against both TNF-alpha and TNF-alpha receptor. Freshly isolated CD4+ T cells from HIV-infected individuals express TNF-alpha on the cell membrane and induce TNF-alpha-mediated immunoglobulin production by B cells. Thus, membrane TNF-alpha seems to be involved in the polyclonal B-cell activation induced by HIV-infected T cells.

A large panel of phytohemagglutinin (PHA)-induced T cell clones (690 in total), established from four different human lymphoid tissues (peripheral blood, tonsils, lymph nodes and spleens) by a high-efficiency cloning technique, was characterized according to their pattern of lymphokine production. The majority of both CD4+ and CD8+ clones from all lymphoid tissues produced interleukin (IL) 2 and/or interferon (IFN)-gamma in response to 24-h stimulation with PHA. In contrast, higher proportions of IL 4-producing clones were found among CD4+ clones from tonsils and spleens than from peripheral blood and lymph nodes, whereas only a minority of CD8+ clones from all lymphoid tissues were found to produce IL 4. It was not possible to divide the CD4+ (helper/inducer) clones on the basis of their pattern of lymphokine activity into two clear-cut groups analogous to Th1 and Th2 helper clones described in mice. Although 21 out of 503 (4%) CD4+ T cell clones produced IL 4, but not IFN-gamma or IL 2, and 208 (41%) produced IL 2 and/or IFN-gamma, but not IL 4, a total number of 185 (37%) CD4+ clones showed the ability to produce IL 4 plus IL 2 and/or IFN-gamma. All types of CD4+ T cells (as classified according to their pattern of lymphokine activity) provided help for IgG production in allogeneic B cells. In contrast, helper function for IgE was detectable only among the IL 4-producing clones.(ABSTRACT TRUNCATED AT 250 WORDS)

In approximately one-third of patients with chronic idiopathic urticaria (CIU), autoantibodies against the high-affinity IgE receptor and/ or against IgE can be detected and a wheal-and-flare response can be provoked by the intradermal injection of autologous serum (ASST). In this study we aimed to further characterize the inflammatory response observed in the subgroup of CIU patients with positive ASST and serum-evoked histamine-release in vitro from basophils in comparison with unaffected skin and healthy donors. An immunohistochemical analysis of infiltrating cells (CD4, MPO, EG1, EG2, tryptase), cytokines (IL-4, IL-5, IFN-gamma), chemokines and chemokine receptors (IL-8, CCR3, CXCR3), and adhesion molecules (ICAM-1, VCAM-1, ELAM-1) was performed on seven selected patients (four males and three females; median age: 45 years; range: 22-57) and five healthy donors. Cytokine evaluation was also performed in five psoriatic patients to obtain an additional control. In spontaneous wheals we observed an increased number of CD4+ T lymphocytes when compared with the controls, and an increased number of neutrophils and eosinophils, whereas mast cells did not show a significant variation. A significant expression for IL-4 and IL-5 could only be observed in lesional skin, while IFN-gamma showed a slight expression in the same site. Chemokine receptors CCR3 and CXCR3 did not show a defined polarized response in either lesional or unaffected skin. An increased expression of all cellular adhesion molecules (CAMs) studied was detected in spontaneous wheals. The lack of a significant difference in the expression of tryptase + mast cells, T lymphocytes, IL-8, CXCR3 and CCR3, a few CAMs between the lesional and unaffected skin of CIU patients suggests a wide immunological activation that involves not only lesional tissues, but possibly extends to the whole of the skin's immune system.