期刊
NATURE MEDICINE
卷 18, 期 3, 页码 422-U184出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nm.2683
关键词
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资金
- US National Cancer Institute Cancer Center [5P30CA014599-35]
- American Cancer Society [ACSLIB112496-RSG]
- American Cancer Society-Illinois Division [07-20]
- Croatian Ministry of Science, Education and Sports [062-0621261-1271]
- Croatian-Israeli Grant
- US National Institutes of Health [R21CA127037, PO1AI082971, K22AI077714]
- Immunology Training Grant [T32]
- University of Chicago [5T32AI007090]
- Cancer Research Foundation
CD4-unhelped CD8(+) T cells are functionally defective T cells primed in the absence of CD4(+) T cell help. Given the co-stimulatory role of natural-killer group 2, member D protein (NKG2D) on CD8(+) T cells, we investigated its ability to rescue these immunologically impotent cells. We demonstrate that augmented co-stimulation through NKG2D during priming paradoxically rescues memory, but not effector, CD8(+) T cell responses. NKG2D-mediated rescue is characterized by reversal of elevated transcription factor T-box expressed in T cells (T-bet) expression and recovery of interleukin-2 and interferon-g production and cytolytic responses. Rescue is abrogated in CD8(+) T cells lacking NKG2D. Augmented co-stimulation through NKG2D confers a high rate of survival to mice lacking CD4(+) T cells in a CD4-dependent influenza model and rescues HIV-specific CD8(+) T cell responses from CD4-deficient HIV-positive donors. These findings demonstrate that augmented co-stimulation through NKG2D is effective in rescuing CD4-unhelped CD8(+) T cells from their pathophysiological fate and may provide therapeutic benefits.
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