@article{8b2874de883e46a7a609f34201be01d6,
title = "NKG2D signaling shifts the balance of CD8 T cells from single cytokine- to polycytokine-producing effector cells",
abstract = "CD8 T cells play a critical role in immunity against intracellular pathogens and cancer. A primary objective of T cell-based vaccine strategies is the induction of durable and effective immune responses. Achieving this goal involves more than simply boosting the numbers of responding T cells. Of particular interest is the induction of CD8 T cells with polycytokine capability, specifically with the ability of CD8 T cells to co-produce IFNγ, TNFα and IL-2. The presence of these polycytokine-producing CD8 T cells correlates strongly with protection against foreign pathogens and cancer. Therefore, approaches capable of inducing such polyfunctional responses are needed. NKG2D engagement on CD8 T cells has been shown to result in increased effector response. However, the manner in which NKG2D engagement results in improved CD8 T cell effector response is unclear. Here we demonstrate in vitro and in vivo that NKG2D engagement by its natural ligand, Rae-1ε, shifts the balance from single cytokine to polycytokine (IL-2, IFNγ, and TFNα) production. These data define a previously unrecognized process in which NKG2D costimulation on CD8 T cells results in improved effector responses.",
keywords = "CD8 T cells, Effector function, NKG2D, Polycytokine",
author = "Kohlhapp, {Frederick J.} and O'Sullivan, {Jeremy A.} and Moore, {Tamson V.} and Andrew Zloza and Guevara-Pati{\~n}o, {Jos{\'e} A.}",
note = "Funding Information: For their kind gifts, we thank: Alan Houghton (pCRAN vector and OVA DNA; Memorial Sloan-Kettering Cancer Center, NY) and Lewis Lanier (Rae-1ε gene; UCSF, CA). This work was supported by the American Cancer Society , USA ( ACSLIB112496-RSG , to J.A.G.), American Cancer Society–Illinois Division , USA (Young Investigator Award Grant #07-20 , to J.A.G.), the National Institutes of Health , USA ( R21CA127037-01A1 to J.A.G.), Cancer Research Foundation (Young Investigator Award, to J.A.G.), R01 CA250514-05 to J.A.G. and the National Institutes of Health , USA (T32 Immunology Training Grant, The University of Chicago, AI07090 to A.Z., F.J.K., and J.A.O.). Volo Family Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. No additional external funding was received for this study. Funding Information: For their kind gifts, we thank: Alan Houghton (pCRAN vector and OVA DNA; Memorial Sloan-Kettering Cancer Center, NY) and Lewis Lanier (Rae-1ε gene; UCSF, CA). This work was supported by the American Cancer Society, USA (ACSLIB112496-RSG, to J.A.G.), American Cancer Society–Illinois Division, USA (Young Investigator Award Grant #07-20, to J.A.G.), the National Institutes of Health, USA (R21CA127037-01A1 to J.A.G.), Cancer Research Foundation (Young Investigator Award, to J.A.G.), R01 CA250514-05 to J.A.G. and the National Institutes of Health, USA (T32 Immunology Training Grant, The University of Chicago, AI07090 to A.Z. F.J.K. and J.A.O.). Volo Family Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. No additional external funding was received for this study. Publisher Copyright: {\textcopyright} 2023",
year = "2023",
month = mar,
doi = "10.1016/j.molimm.2022.12.013",
language = "English (US)",
volume = "155",
pages = "1--6",
journal = "Immunochemistry",
issn = "0161-5890",
publisher = "Elsevier Limited",
}
