title: Interleukin-2 rescues helpless effector CD8+ T cells by diminishing the susceptibility to TRAIL mediated death.
abstract: 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.
authors.affiliation: Department of Cellular Immunology, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA. m.wolkers@sanquin.nl
authors.forename: Monika C
authors.initials: MC
authors.lastname: Wolkers
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Bensinger
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Green
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Schoenberger
authors.forename: Edith M
authors.initials: EM
authors.lastname: Janssen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D016923:Cell Death / Q000276:immunology; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism*; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism*
chemical_list: D016207:Cytokines; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D053221:TNF-Related Apoptosis-Inducing Ligand