@article{1e72b6d2f8994c22b299a2012980e004,
title = "Immunomodulatory effects of cytokine-induced expansion of cytotoxic lymphocytes in a mouse model of lupus-like disease",
abstract = "Background aims: Certain therapies (e.g., daclizumab) that promote expansion of natural killer (NK) cells are associated with clinical amelioration of disease in the context of multiple sclerosis and associated mouse models. The clinical benefits are putatively attributable to an enhanced capacity of NK cells to kill activated pathogenic T cells. Whether a parallel approach will also be effective in systemic lupus erythematosus (lupus), a multi-organ autoimmune disease driven by aberrant responses of self-reactive T and B cells, is unclear. Methods: In the present study, the authors assess the therapeutic impact of IL-2- and IL-15-based strategies for expanding NK cells on measures of lupus-like disease in a mouse model. Results: Unexpectedly, cytokine-mediated expansion of cytotoxic lymphocytes aggravated immunological measures of lupus-like disease. Depletion studies revealed that the negative effects of these cytokine-based regimens can largely be attributed to expansion of CD8 T cells rather than NK cells. Conclusions: These results provoke caution in the use of cytokine-based therapeutics to treat co-morbid cancers in patients with lupus and highlight the need for new methods to selectively expand NK cells to further assess their clinical value in autoimmune disease.",
keywords = "CD8 T cell, IL-15, IL-2, natural killer, systemic lupus erythematosus, therapy",
author = "Reighard, {Seth D.} and Durga Krishnamurthy and Hilal Cevik and Ochayon, {David E.} and Ayad Ali and Harsha Seelamneni and Brunner, {Hermine I.} and Waggoner, {Stephen N.}",
note = "Funding Information: Investigators on this project were supported by National Institutes of Health grants DA038017 , AI148080 , AR073228 , AI145304 (SNW), T32GM063483 , T32AI118697 (SDR and AA), AR071651 and AR076316 (HIB). Additional support was provided to SNW and HIB by Cincinnati Children's Research Foundation, the Cincinnati Center for Pediatric Genomics and the Dr Ralph and Marian Falk Medical Research Trust. SDR was also supported by a Gina Finzi Memorial Student Fellowship from the Lupus Foundation. DEO is supported by an American Heart Association Fellowship and the Arnold Strauss Fellowship. AA is supported by the Albert Ryan Fellowship. The Cincinnati Children's Flow Cytometry Core is supported by National Institutes of Health grants AR047363 , AR070549 , DK078392 , DK090971 , S10OD025045 and S10OD023410 . N-803 and guidance in use of this drug were kindly provided by the team at ImmunityBio (formerly known as Altor BioScience). Funding Information: Investigators on this project were supported by National Institutes of Health grants DA038017, AI148080, AR073228, AI145304 (SNW), T32GM063483, T32AI118697 (SDR and AA), AR071651 and AR076316 (HIB). Additional support was provided to SNW and HIB by Cincinnati Children's Research Foundation, the Cincinnati Center for Pediatric Genomics and the Dr Ralph and Marian Falk Medical Research Trust. SDR was also supported by a Gina Finzi Memorial Student Fellowship from the Lupus Foundation. DEO is supported by an American Heart Association Fellowship and the Arnold Strauss Fellowship. AA is supported by the Albert Ryan Fellowship. The Cincinnati Children's Flow Cytometry Core is supported by National Institutes of Health grants AR047363, AR070549, DK078392, DK090971, S10OD025045 and S10OD023410. N-803 and guidance in use of this drug were kindly provided by the team at ImmunityBio (formerly known as Altor BioScience). The authors have no commercial, proprietary or financial interest in the products or companies described in this article. Conception and design of the study: SNW and SDR. Acquisition of data: SDR, DK, HC, DEO, AA, and HS. Analysis and interpretation of data: SDR, DK, HC, DEO, AA, HS, and SNW. Drafting or revising the manuscript: SDR, DK, HC, DEO, AA, HS, HIB, and SNW. All authors have approved the final article. The authors thank J. Klarquist and E. Janssen for expertise and for generating the bm12/CD45.1 mouse line that was used for the disease model. The authors also thank Q. Ma, P. Devarajan and W. Shao for assistance in evaluating lupus-like disease. Publisher Copyright: {\textcopyright} 2020 International Society for Cell & Gene Therapy",
year = "2021",
month = jan,
day = "1",
doi = "10.1016/j.jcyt.2020.09.003",
language = "English",
volume = "23",
pages = "37--45",
journal = "Cytotherapy",
issn = "1465-3249",
publisher = "Elsevier Inc.",
number = "1",
}
