41The transcription factor Eomesodermin (EOMES) promotes IL-10 production of CD4 + T-cells, which has 42 been linked to immunosuppressive and cytotoxic activities. We detected EOMES-expressing CD4 + T-43 cells in lymph node samples of patients with chronic lymphocytic leukemia (CLL) or diffuse large B-cell 44 lymphoma. This was in line with an observed expansion of EOMES-positive CD4 + T-cells in leukemic Eµ-45 TCL1 mice, a well-established model of CLL, and upon adoptive transfer of TCL1 leukemia in mice. 46Transcriptome and flow cytometry analyses revealed that EOMES does not only drive the transcription 47 of IL-10, but rather controls a unique differentiation program in CD4 + T-cells. Moreover, EOMES was 48 necessary for the accumulation of a specific CD4 + T-cell subset that expresses IFNγ and IL-10, as well 49 as inhibitory receptors, like PD-1 and LAG3. T-cell transfer studies in leukopenic Rag2 -/mice showed 50 that EOMES-deficient CD4 + T-cells were inferior in controlling TCL1 leukemia development compared 51 to wildtype T-cells, even though expansion of Eomes -/-CD4 + T-cells was observed. We further showed 52 that control of TCL1 leukemia was driven by IL-10 receptor-mediated signals, as Il10rb-deficient CD4 + 53 T-cells showed impaired anti-leukemia activity. Altogether, our data suggest that IL-10 producing PD-54
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