Lack of IL-21 signal attenuates graft-versus-leukemia effect in the absence of CD8 T-cells View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2011-01-24

AUTHORS

A Meguro, K Ozaki, K Hatanaka, I Oh, K Sudo, T Ohmori, H Matsu, R Tatara, K Sato, Y Sakata, S Nakae, W J Leonard, K Ozawa

ABSTRACT

Previously, we have shown that IL-21R−/− splenocytes ameliorate GVHD as compared with wild-type splenocytes. Here, we investigated whether or not IL-21R−/− splenocytes diminish the graft-versus-leukemia (GVL) effect. Surprisingly, IL-21R−/− splenocytes efficiently eliminate leukemic cells as well as wild-type splenocytes, suggesting the retention of GVL effects in the absence of IL-21 signaling. To compare the GVL effect between IL-21R−/− and wild-type cells, we titrated the number of splenocytes required for the elimination of leukemic cells and found that the threshold of GVL effect was obtained between 5 × 105 and 5 × 106 with both types of splenocytes. Cotransplantation with CD8-depleted splenocytes but not with purified CD8 T-cells resulted in a significant reduction in anti-leukemic effect of IL-21R−/− cells compared with wild-type cells, suggesting that the lack of IL-21 signaling primarily impairs CD4 T-cell rather than CD8 T-cell function and the comparable GVL effect with IL-21R−/− bulk splenocytes results from cooperative compensation by CD8 T-cells. More... »

PAGES

1557-1565

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/bmt.2010.342

DOI

http://dx.doi.org/10.1038/bmt.2010.342

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1033728881

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/21258423


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