1. Lack of IL-21 signal attenuates graft-versus-leukemia effect in the absence of CD8 T-cells.
- Author
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Meguro, A, Ozaki, K, Hatanaka, K, Oh, I, Sudo, K, Ohmori, T, Matsu, H, Tatara, R, Sato, K, Sakata, Y, Nakae, S, Leonard, W J, and Ozawa, K
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LEUKEMIA ,T cells ,LEUCOCYTOSIS ,LYMPHOCYTES ,GRAFT versus host disease - 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. [ABSTRACT FROM AUTHOR]- Published
- 2011
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