Project name: Mus musculus

Description: IL-2 and IL-21 are closely related cytokines that might have arisen by gene duplication. Both cytokines promote the function of effector CD8+ T cells, but their distinct effects on antigen-driven differentiation of naïve CD8+ T cells into effector CD8+ T cells are not clearly understood. We found that antigen-induced expression of eomesodermin and maturation of naïve CD8+ T cells into granzyme B and CD44 expressing effector CD8+ T cells was enhanced by IL-2, but, unexpectedly, suppressed by IL-21. Furthermore, IL-21 repressed expression of IL-2Ra and inhibited IL-2-mediated acquisition of a cytolytic CD8+ T cell phenotype. Despite its inhibitory effects, IL-21 did not induce anergy, but instead potently enhanced the capacity of cells to mediate tumor regression upon adoptive transfer. In contrast, IL-2, surprisingly, impaired the subsequent anti-tumor function of transferred cells. Gene expression studies revealed a distinct IL-21-program that was characterized phenotypically by increased expression of L-selectin and functionally by enhanced anti-tumor immunity that was not reversed by secondary in vitro stimulation with antigen and IL-2. Thus, the efficacy of CD8+ T cells for adoptive immunotherapy can be influenced by opposing differentiation programs conferred by IL-2 and IL-21, a finding with important implications for the development of cellular cancer therapies.Two-condition experiment: Cytokine-exposed t-cells subsequentially restimulated without cytokine vs. control t-cells without cytokine subsquentially restimulated without cytokine. 3 independent experiments - 1 with experimental RNA labeled with Cy5, control with Cy3, and 2 with dyes-swappedKeywords: Cytokine exposure comparisonOverall design: Comparitive analysis of cytokine effects on lymphocyte gene expression.GSM265712.gpr (S89_1_IL2_0.gpr): Cy3 - control, Cy5 - experimentalGSM265713.gpr (S90_1_IL15_0.gpr): Cy3 - control, Cy5 - experimentalGSM265714.gpr (S91_1_IL21_0.gpr): Cy3 - control, Cy5 - experimentalGSM265715.gpr (S27_2_0_IL2.gpr): Cy3 - experimental, Cy5 - controlGSM265716.gpr (S29_2_0_IL15.gpr): Cy3 - experimental, Cy5 - controlGSM265717.gpr (S30_2_0_IL21.gpr): Cy3 - experimental, Cy5 - controlGSM265718.gpr (S31_3_0_IL2.gpr): Cy3 - experimental, Cy5 - controlGSM265719.gpr (S33_3_0_IL15.gpr): Cy3 - experimental, Cy5 - control

Data type: Transcriptome or Gene expression

Sample scope: Multiisolate

Relevance: ModelOrganism

Release date: 2008-02-13

Last updated: 2008-02-06