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 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 2" - "Export Date: 20 April 2011" - "CODEN: BLOOA" - "Source: Scopus" |
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