Description: Background— Self-care training can reduce hospitalization for heart failure (HF), and more intensive intervention may benefit more vulnerable patients, including those with low literacy. Methods and Results— A 1-year, multisite, randomized, controlled comparative effectiveness trial with 605 patients with HF was conducted. Those randomized to a single session received a 40-minute in-person, literacy-sensitive training; the multisession group received the same initial training and then ongoing telephone-based support. The primary outcome was combined incidence of all-cause hospitalization or death; secondary outcomes included HF-related hospitalization and HF-related quality of life, with prespecified stratification by literacy. Overall, the incidence of all-cause hospitalization and death did not differ between intervention groups (incidence rate ratio, 1.01; 95% confidence interval, 0.83–1.22). The effect of multisession training compared with single-session training differed by literacy group: Among those with low literacy, the multisession training yielded a lower incidence of all-cause hospitalization and death (incidence rate ratio, 0.75; 95% confidence interval, 0.45–1.25), and among those with higher literacy, the multisession intervention yielded a higher incidence (incidence rate ratio, 1.22; 95% confidence interval, 0.99–1.50; interaction P =0.048). For HF-related hospitalization, among those with low literacy, multisession training yielded a lower incidence (incidence rate ratio, 0.53; 95% confidence interval, 0.25–1.12), and among those with higher literacy, it yielded a higher incidence (incidence rate ratio, 1.32; 95% confidence interval, 0.92–1.88; interaction P =0.005). HF-related quality of life improved more for patients receiving multisession than for those receiving single-session interventions at 1 and 6 months, but the difference at 12 months was smaller. Effects on HF-related quality of life did not differ by literacy. Conclusions— Overall, an intensive multisession intervention did not change clinical outcomes compared with a single-session intervention. People with low literacy appear to benefit more from multisession interventions than people with higher literacy. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00378950.

Description: The thymus generates T cells with diverse specificities and functions. To assess the contribution of cytokine receptors to the differentiation of T cell subsets in the thymus, we constructed conditional knockout mice in which IL-7Rα or common cytokine receptor chain ( c ) genes were deleted in thymocytes just before positive selection. We found that c expression was required to signal the differentiation of MHC class I (MHC-I)–specific thymocytes into CD8 + cytotoxic lineage T cells and into invariant natural killer T cells but did not signal the differentiation of MHC class II (MHC-II)–specific thymocytes into CD4 + T cells, even into regulatory Foxp3 + CD4 + T cells which require c signals for survival. Importantly, IL-7 and IL-15 were identified as the cytokines responsible for CD8 + cytotoxic T cell lineage specification in vivo. Additionally, we found that small numbers of aberrant CD8 + T cells expressing Runx3d could arise without c signaling, but these cells were developmentally arrested before expressing cytotoxic lineage genes. Thus, c -transduced cytokine signals are required for cytotoxic lineage specification in the thymus and for inducing the differentiation of MHC-I–selected thymocytes into functionally mature T cells.

Description: Interleukin-7 receptor α (IL-7Rα) is essential for T cell survival and differentiation. Glucocorticoids are potent enhancers of IL-7Rα expression with diverse roles in T cell biology. Here we identify the transcriptional repressor, growth factor independent-1 (Gfi1), as a novel intermediary in glucocorticoid-induced IL-7Rα up-regulation. We found Gfi1 to be a major inhibitory target of dexamethasone by microarray expression profiling of 3B4.15 T-hybridoma cells. Concordantly, retroviral transduction of Gfi1 significantly blunted IL-7Rα up-regulation by dexamethasone. To further assess the role of Gfi1 in vivo, we generated bacterial artificial chromosome (BAC) transgenic mice, in which a modified Il7r locus expresses GFP to report Il7r gene transcription. By introducing this BAC reporter transgene into either Gfi1-deficient or Gfi1-transgenic mice, we document in vivo that IL-7Rα transcription is up-regulated in the absence of Gfi1 and down-regulated when Gfi1 is overexpressed. Strikingly, the in vivo regulatory role of Gfi1 was specific for CD8+, and not CD4+ T cells or immature thymocytes. These results identify Gfi1 as a specific transcriptional repressor of the Il7r gene in CD8 T lymphocytes in vivo.