Resistance to Fas-mediated T cell apoptosis in asthma

Sundararajan Jayaraman, Mario Castro, Mary O'Sullivan, M. Janice Bragdon, Michael J. Holtzman

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Abstract

Over activation of CD4+ T cells in the peripheral blood and airway tissues is characteristic of asthma; therefore, we investigated whether activated T cells from asthmatic subjects have altered apoptotic potential through the Fas death receptor. We found that mitogen-stimulated peripheral blood T cells of asthmatic subjects expressed cell surface Fas, but failed to undergo the normal degree of apoptosis after Fas receptor ligation. T cells from asthmatics exhibited normal apoptotic responses to γ-irradiation (dependent on IL-1 converting enzyme family proteases), ceramide, and mitogen challenge, suggesting functional integrity of the apoptotic pathway. Furthermore, the defect in Fas-dependent apoptosis was overcome by prestimulation with allogeneic accessory cells instead of mitogen. Taken together, the findings suggest that selective resistance to Fas-dependent apoptosis reflects altered Ag-driven, accessory cell-dependent signaling and that ineffective activation of Fas signal transduction may contribute to T cell-dependent immunoinflammation in asthma.

Original languageEnglish
Pages (from-to)1717-1722
Number of pages6
JournalJournal of Immunology
Volume162
Issue number3
StatePublished - Feb 1 1999

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    Jayaraman, S., Castro, M., O'Sullivan, M., Bragdon, M. J., & Holtzman, M. J. (1999). Resistance to Fas-mediated T cell apoptosis in asthma. Journal of Immunology, 162(3), 1717-1722.