학술논문
NKG2D signaling on CD8+ T cells represses T-bet and rescues CD4-unhelped CD8+ T cell memory recall but not effector responses.
Document Type
Article
Author
Zloza, Andrew; Kohlhapp, Frederick J; Lyons, Gretchen E; Schenkel, Jason M; Moore, Tamson V; Lacek, Andrew T; O'Sullivan, Jeremy A; Varanasi, Vineeth; Williams, Jesse W; Jagoda, Michael C; Bellavance, Emily C; Marzo, Amanda L; Thomas, Paul G; Zafirova, Biljana; Poli?, Bojan; Al-Harthi, Lena; Sperling, Anne I; Guevara-Patiño, José A
Source
Subject
*KILLER cells
*CD4 antigen
*T cells
*INTERLEUKIN-2
*INTERFERONS
*IMMUNOLOGY
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Language
ISSN
1078-8956
Abstract
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-? 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. [ABSTRACT FROM AUTHOR]