Interleukin-2 rescues helpless effector CD8+ T cells by diminishing the susceptibility to TRAIL mediated death

Department of Cellular Immunology, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA.
Immunology letters (Impact Factor: 2.51). 05/2011; 139(1-2):25-32. DOI: 10.1016/j.imlet.2011.04.011
Source: PubMed


CD8(+) T cells primed in the absence of CD4(+) T cell help are programmed to produce TRAIL, which results in Death receptor (DR5) mediated apoptosis upon restimulation. Here, we studied whether these 'helpless' effector CD8(+) T cells are consigned to an apoptotic fate or whether their helpless program can be altered by inflammatory or growth cytokines. We found that helpless CD8(+) T cells regained their full proliferative and functional capacity only when IL-2 was added to cell cultures, while IL-7 and IL-15, two common gamma chain cytokines associated with CD8(+) T cell homeostasis and memory, could only partly restore secondary expansion in helpless CD8(+) T cells. Recovery of functional CD8(+) T cell immunity by IL-2 was concomitant with induction of IL2Rα (CD25) expression, downregulation of TRAIL, and the upregulation of anti-apoptotic molecules Bcl-2 and FLIP. The addition of IL-2 to helpless CD8(+) T cells also interfered with DR5-mediated apoptosis induction, indicating that IL-2 affects several components of the TRAIL-DR5 pathway. Collectively, these data demonstrate that the helpless phenotype is not fixed, and that IL-2R signaling at the time of reactivation can play an important role in restoring CD8(+) T cell function.

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Available from: Edith M Janssen
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    • "Importantly, evidence has been provided that IL-12R does not signal through PI3K, and also fails to induce EGR-1 [22] [23]. This is also in line with our previous findings that IL-2 and IL-15 triggering of T cells affects TRAIL expression in murine T cells in a Nab2-dependent manner, while IL-12 triggering fails to do so [24]. Of note, also other early activation gene family members such as c-fos and junB, and the transcription factor AP-1 are induced upon IL-2R signalling, but not upon IL-12R-mediated signalling [23]. "
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