IL-7 and IL-21 are superior to IL-2 and IL-15 in promoting human T cell-mediated rejection of systemic lymphoma in immunodeficient mice Journal Article

Authors: Markley, J. C.; Sadelain, M.
Article Title: IL-7 and IL-21 are superior to IL-2 and IL-15 in promoting human T cell-mediated rejection of systemic lymphoma in immunodeficient mice
Abstract: The γc-cytokines are critical regulators of immunity and possess both overlapping and distinctive functions. However, comparative studies of their pleiotropic effects on human T cell-mediated tumor rejection are lacking. In a xenogeneic adoptive transfer model, we have compared the therapeutic potency of CD19-specific human primary T cells that constitutively express interleukin-2 (IL-2), IL-7, IL-15, or IL-21. We demonstrate that each cytokine enhanced the eradication of systemic CD19+ B-cell malignancies in nonobese diabetic/severe combined immunodeficient (NOD/SCID)/γcnull mice with markedly different efficacies and through singularly distinct mechanisms. IL-7- and IL-21-transduced T cells were most efficacious in vivo, although their effector functions were not as enhanced as IL-2- and IL-15-transduced T cells. IL-7 best sustained in vitro T-cell accumulation in response to repeated antigenic stimulation, but did not promote long-term T-cell persistence in vivo. Both IL-15 and IL-21 overexpression supported long-term T-cell persistence in treated mice; however, the memory T cells found 100 days after adoptive transfer were phenotypically dissimilar, resembling central memory and effector memory T cells, respectively. These results support the use of γc- cytokines in cancer immunotherapy, and establish that there exists more than 1 human T-cell memory phenotype associated with long-term tumor immunity. © 2010 by The American Society of Hematology.
Keywords: controlled study; protein expression; human cell; nonhuman; t lymphocyte; t-lymphocytes; mouse; phenotype; animals; mice; interleukin 2; interleukin 21; interleukin 7; animal experiment; animal model; antineoplastic activity; mice, scid; lymphoma, b-cell; cytokine; lymphoma; transplantation, heterologous; adoptive transfer; effector cell; neoplasm transplantation; mice, inbred nod; tumor rejection; cell strain 3t3; interleukin 15; cd19 antigen; scid mouse; antigens, cd19; immunologic memory; interleukins; interleukin-2; interleukin-7; memory t lymphocyte; interleukin-15
Journal Title: Blood
Volume: 115
Issue: 17
ISSN: 0006-4971
Publisher: American Society of Hematology  
Date Published: 2010-04-29
Start Page: 3508
End Page: 3519
Language: English
DOI: 10.1182/blood-2009-09-241398
PUBMED: 20190192
PROVIDER: scopus
PMCID: PMC2867264
Notes: --- - "Cited By (since 1996): 2" - "Export Date: 20 April 2011" - "CODEN: BLOOA" - "Source: Scopus"
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  1. Michel W J Sadelain
    452 Sadelain