Human T cells with a type-2 cytokine profile are resistant to apoptosis induced by primary activation: consequences for immunopathogenesis.
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-gamma)) 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-gamma 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.
Carbonari
M
M
Department of Clinical Medicine, University of Rome 'La Sapienza', Rome, Italy.
Tedesco
T
T
Del Porto
P
P
Paganelli
R
R
Fiorilli
M
M
D000163:Acquired Immunodeficiency Syndrome / Q000097:blood; D017209:Apoptosis; D015704:CD4 Antigens / Q000097:blood; D016827:CD8 Antigens / Q000097:blood; D002478:Cells, Cultured; D004802:Eosinophilia / Q000097:blood; D006801:Humans; D006942:Hypergammaglobulinemia / Q000097:blood; D007154:Immune System Diseases / Q000503:physiopathology*; D007073:Immunoglobulin E / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000502:physiology*
D015704:CD4 Antigens; D016827:CD8 Antigens; D019253:Proto-Oncogene Proteins c-bcl-2; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma