| First Author | Zloza A | Year | 2012 |
| Journal | Nat Med | Volume | 18 |
| Issue | 3 | Pages | 422-8 |
| PubMed ID | 22366950 | Mgi Jnum | J:181623 |
| Mgi Id | MGI:5312159 | Doi | 10.1038/nm.2683 |
| Citation | Zloza A, et al. (2012) NKG2D signaling on CD8(+) T cells represses T-bet and rescues CD4-unhelped CD8(+) T cell memory recall but not effector responses. Nat Med 18(3):422-8 |
| abstractText | 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-gamma 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. |
