Human T cells with a type-2 cytokine profile are resistant to apoptosis induced by primary activation: consequences for immunopathogenesis
M. Carbonari, T. Tedesco, P. Del Porto,
R. Paganelli, M. Fiorilli,
P. Del Porto
Department of Cellular and Developmental Biology, University of Rome ‘La Sapienza’, Rome, Italy
Search for more papers by this authorM. Carbonari, T. Tedesco, P. Del Porto,
R. Paganelli, M. Fiorilli,
P. Del Porto
Department of Cellular and Developmental Biology, University of Rome ‘La Sapienza’, Rome, Italy
Search for more papers by this author Massimo Fiorilli MD, Dipartimento di Medicina Clinica, Università di Roma ‘La Sapienza’, Viale dell'Università 37, 00185 Rome, Italy.E-mail:
[email protected]
Abstract
The mechanisms leading to a relative dominance of T cells producing type 2 cytokines in certain human immune disorders are still unclear. We investigated the relative susceptibility to apoptosis induced by primary in vitro activation of human type 1 (producing interferon-gamma (IFN-γ)) or type 2 (producing IL-4) T cells. Peripheral blood lymphocytes were isolated from patients with immune disorders characterized by expansion of type 2 cells (four with AIDS and hyper-IgE/hypereosinophilia, one with Churg–Strauss syndrome, and one with idiopathic hypereosinophilic syndrome) or from individuals with normal cytokine balances. Cells were stimulated for 16 h with ionomycin and phorbol ester, and apoptosis of cytokine-producing cells was assessed by flow cytometry. T cells with a type-2 cytokine profile, i.e. producing IL-4 alone, were significantly more resistant to activation-induced apoptosis than those producing IFN-γ alone. This was observed in AIDS patients, whose type 2 cells were mostly CD8+, as well as in the patients with Churg–Strauss and with hypereosinophilic syndrome. CD4+ and CD8+ IL-4-producing cells were equally resistant to apoptosis. Lower susceptibility to apoptosis of type-2 T cells was also observed in subjects with normal cytokine balances. Bcl-2 expression was high in type-2 cells and in viable type-1 cells, whereas it was low in apoptotic type-1 cells. Resistance to activation-induced apoptosis may explain the expansion of cells producing type-2 cytokines in certain immune disorders.
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