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OBJECTIVE. To explore tumor necrosis factor (TNF)-induced apoptosis in neutrophils from patients with TNF receptor-associated periodic syndrome (TRAPS) and to correlate the results with the different kinds of TNFRSF1A mutations. METHODS: Two hundred sixty-five patients with clinically suspected inherited autoinflammatory syndrome were screened for mutations of the TNFRSF1A gene. Neutrophils were isolated from heparinized blood by dextran sedimentation and incubated with and without cycloheximide (CHX) and TNFalpha. Cell apoptosis was assessed by human annexin V binding, and caspase 8 activation was assessed by flow cytometry. RESULTS: Twenty-one patients were found to carry a variant of the TNFRSF1A gene: 13 patients had an R92Q substitution, and 8 patients presented other missense substitutions, 1 splicing mutation, and 1 in-frame interstitial deletion. Neutrophil stimulation with TNF and CHX was associated with induction of apoptosis in 12 normal controls and in 10 subjects with the R92Q mutation. Conversely, neutrophils from 8 TRAPS patients with mutations of cysteine or threonine residues or interstitial deletion did not show any induction of apoptosis after stimulation. The incidence of the R92Q mutation among patients with recurrent autoinflammatory syndromes was similar to that observed in the normal population. CONCLUSION: Resistance to TNF-mediated apoptosis is a feature in TRAPS patients who have mutations of cysteine residues or interstitial deletion, and may play a pathogenic role. The R92Q mutation does not appear to be significantly associated with TRAPS. [ABSTRACT FROM AUTHOR]

In this study we analysed the potential of highly purified polyclonal TcR αβ+, TcRγδ+ and CD3- NK cells, to produce lymphokines in response lo mitogenic stimulation. RNA hybridizations were performed to detect with high sensitivity the induction of multiple lymphokine genes. Upon stimulation with lectin and phorbol ester TcR γδ+ lymphocytes expressed the same set of lymphokine genes as the TcR αβ+ lymphocytes, which included IL-2,-3,-4,-5, GM-CSF. TNFα and β, IFNγ. In contrast, a more limited set of lymphokine genes (GM-CSF, TNFα and β, IFNγ) was induced in activated CD3- NK cells, thus indicating that this subpopulation of cells may display different regulatory functions, with respect to CD3+ T lymphocytes. [ABSTRACT FROM AUTHOR]