Explore the vast range of titles available.

Lanier and colleagues systematically define the transcriptome of mouse natural killer cells in several contexts, including activation states and relative to all other lymphocyte and myeloid populations profiled by the Immunological Genome Project consortium. Using whole-genome microarray data sets of the Immunological Genome Project, we demonstrate a closer transcriptional relationship between NK cells and T cells than between any other leukocytes, distinguished by their shared expression of genes encoding molecules with similar signaling functions. Whereas resting NK cells are known to share expression of a few genes with cytotoxic CD8 + T cells, our transcriptome-wide analysis demonstrates that the commonalities extend to hundreds of genes, many encoding molecules with unknown functions. Resting NK cells demonstrate a 'preprimed' state compared with naive T cells, which allows NK cells to respond more rapidly to viral infection. Collectively, our data provide a global context for known and previously unknown molecular aspects of NK cell identity and function by delineating the genome-wide repertoire of gene expression of NK cells in various states.

A patient with refractory metastatic melanoma had a complete remission after an infusion of cells from an in vitro–generated clone of autologous CD4+ T cells with specificity for the melanoma-associated NY-ESO-1 antigen. A patient with refractory metastatic melanoma had a complete remission after an infusion of cells from an in vitro–generated clone of autologous CD4+ T cells with specificity for the melanoma-associated NY-ESO-1 antigen. CD8+ cytotoxic T cells can be harvested from a patient with cancer, expanded in vitro, selected for specificity against a tumor-associated antigen, and infused back into the patient. Such autologous T cells have been shown in clinical trials to have a beneficial effect in some patients with cancer. 1 – 5 The cytotoxic antitumor effect of CD8+ T cells depends on CD4+ T cells, which provide CD8+ T cells with growth factors such as interleukin-2 and can mediate the destruction of tumor cells either directly or indirectly. 5 – 8 Growth factors such as interleukin-2 can act in an autocrine manner, which in principle . . .

Complete T cell development requires postthymic maturation, and we investigated the influence of this ontological period on the CD8 T cell response to infection by comparing responses of mature CD8 T cells with those of recent thymic emigrants (RTEs). When activated with a noninflammatory stimulus or a bacterial or viral pathogen, CD8 RTEs generated a lower proportion of cytokine-producing effector cells and long-lived memory precursors compared with their mature counterparts. Although peripheral T cell maturation is complete within several weeks after thymic egress, RTE-derived memory cells continued to express inappropriate levels of memory cell markers and display an altered pattern of cytokine production, even 8 weeks after infection. When rechallenged, RTE-derived memory cells generated secondary effector cells that were phenotypically and functionally equivalent to those generated by their mature counterparts. The defects at the effector and memory stages were not associated with differences in the expression of T cell receptor-, costimulation-, or activation-associated cell surface markers yet were associated with lower Ly6C expression levels at the effector stage. This work demonstrates that the stage of postthymic maturation influences cell fate decisions and cytokine profiles of stimulated CD8 T cells, with repercussions that are apparent long after cells have progressed from the RTE compartment.

Key Points Recent thymic emigrants (RTEs), the youngest peripheral T cells, undergo progressive phenotypic and functional maturation during their first few weeks in the peripheral lymphoid tissue. Here, RTEs and their more mature, although still naive, T cell counterparts occupy largely overlapping niches. RTEs are a functionally distinct subset of the peripheral T cell pool, characterized by reduced cytokine and transcription factor expression compared with mature naive T cells. Post-thymic maturation requires thymic egress and access to secondary lymphoid organs; however, the molecular trigger(s) that drive RTE maturation are still unknown, although the transcriptional repressor NKAP may be required. RTEs are not simply the cellular midpoint between single-positive progenitor thymocytes and mature peripheral T cells, and this suggests that transit through this developmental stage is necessary. Post-thymic maturation may be crucial for ensuring that RTEs are self tolerant or that they are fit to receive homeostatic signals. Recent thymic emigrants (RTEs) are a population of T cells that undergo maturation in the periphery and are functionally distinct from mature naive T cells. These cells constitute a major proportion of the T cell pool in neonates and in adults recovering from lymphoablation. This article describes what is known, and what remains to be discovered, about RTEs. T cell maturation was once thought to occur entirely within the thymus. Now, evidence is mounting that the youngest peripheral T cells in both mice and humans comprise a distinct population from their more mature, yet still naive, counterparts. These cells, termed recent thymic emigrants (RTEs), undergo a process of post-thymic maturation that can be monitored at the levels of cell phenotype and immune function. Understanding this final maturation step in the process of generating useful and safe T cells is of clinical relevance, given that RTEs are over-represented in neonates and in adults recovering from lymphopenia. Post-thymic maturation may function to ensure T cell fitness and self tolerance.

Using whole-genome microarray datasets of the Immunological Genome Project, we demonstrate a closer transcriptional relationship between NK and T cells than any other leukocytes, distinguished by their expression of similar signaling functions. While resting NK cells were known to share expression of a few genes with cytotoxic CD8+ T cells, transcriptome-wide analysis demonstrates that the commonalities extend to hundreds of genes, many with unknown functions. The NK cell response to viral infection is dampened relative to cytotoxic CD8+ T cells, in part due to their “pre-primed” state. Collectively, the data provide global context for known and novel molecular aspects of NK cell identity and function by delineating the genome-wide repertoire of gene expression of NK cells in various states.

Complete T cell development requires postthymic maturation, and we investigated the influence of this ontological period on the CD8 T cell response to infection by comparing responses of mature CD8 T cells with those of recent thymic emigrants (RTEs). When activated with a noninflammatory stimulus or a bacterial or viral pathogen, CD8 RTEs generated a lower proportion of cytokine-producing effector cells and long-lived memory precursors compared with their mature counterparts. Although peripheral T cell maturation is complete within several weeks after thymic egress, RTE-derived memory cells continued to express inappropriate levels of memory cell markers and display an altered pattern of cytokine production, even 8 weeks after infection. When rechallenged, RTE-derived memory cells generated secondary effector cells that were phenotypically and functionally equivalent to those generated by their mature counterparts. The defects at the effector and memory stages were not associated with differences in the expression of T cell receptor-, costimulation-, or activation-associated cell surface markers yet were associated with lower Ly6C expression levels at the effector stage. This work demonstrates that the stage of postthymic maturation influences cell fate decisions and cytokine profiles of stimulated CD8 T cells, with repercussions that are apparent long after cells have progressed from the RTE compartment.

We developed an in vitro method for isolating and expanding autologous CD4+ T-cell clones with specificity for the melanoma-associated antigen NY-ESO-1. We infused these cells into a patient with refractory metastatic melanoma who had not undergone any previous conditioning or cytokine treatment. We show that the transferred CD4+ T cells mediated a durable clinical remission and led to endogenous responses against melanoma antigens other than NY-ESO-1.

Recent thymic emigrants (RTEs) are the youngest T cells in the periphery, having recently completed the complex process of intra-thymic development. RTEs are an important source of new TCR specificities throughout life, and they help reconstitute the peripheral T cell pool in neonates and those suffering from lymphopenic conditions. RTEs exit the thymus in an immature state, undergoing both phenotypic and functional maturation during the first 3 weeks they reside in the periphery. CD4+ RTEs exhibit defects in proliferation, IL-2 production and CD25 upregulation compared to their more mature, but still naïve (MN), peripheral T cell counterparts. The capacity for CD4 + RTEs to differentiate into the various T helper (Th) lineages and generate a mature Th effector response is still poorly understood. Using a well-controlled in vitro polarization scheme, we show here that CD4+ RTEs are defective in Th0, Th1, Th17 and regulatory T cell lineage commitment, with dampened cytokine production and transcription factor expression. In contrast, in a Th2 environment, CD4+ RTES are biased toward this lineage both in vitro and in vivo, with more robust IL-4, IL-5 and IL-13 production than their MN T cell counterparts. Co-culture experiments demonstrate that MN T cells influence neighboring RTEs in their Th responses In adoptive hosts, CD4 + RTEs drive production of the Th2-associated antibody isotype IgG1 and mediate airway inflammatory disease. Despite diminished Th1 effector function in vitro, CD4+ RTEs can overcome their functional defects under certain conditions in vivo. The distinct Th effector function exhibited by RTEs likely results from dampened negative regulation of the Th2 lineage by diminished levels of T-bet, a key Th1 transcription factor. CD4+ RTEs exhibit a unique signaling \"signature\" with differential gene expression and epigenetic regulation compared to MN T cells. CD4+ RTEs thus represent a peripheral T cell population with a distinct interpretation of, and response to, immunological cues. These characteristics may be beneficial during the post-thymic maturation period to avoid inappropriate immune responses, particularly in lymphopenic neonates and adults.

The Summary of Notifiable Infectious Diseases and Conditions-United States, 2014 (hereafter referred to as the summary) contains the official statistics, in tabular and graphic form, for the reported occurrence of nationally notifiable infectious diseases and conditions in the United States for 2014. Unless otherwise noted, data are final totals for 2014 reported as of June 30, 2015. These statistics are collected and compiled from reports sent by U.S. state and territory, New York City, and District of Columbia health departments to the National Notifiable Diseases Surveillance System (NNDSS), which is operated by CDC in collaboration with the Council of State and Territorial Epidemiologists (CSTE). This summary is available at http://www.cdc.gov/mmwr/mmwr_nd/index.html. This site also includes summary publications from previous years.

Data from two surveys are used in this DataWatch to explore Americans' understanding of their health insurance. First, data from a national survey of consumers are used to examine if people with private health insurance correctly report their coverage for six services. Second, information from an evaluation of a pilot project of subsidized insurance in New York is used to investigate how well newly insured persons understand their coverage. Based on these surveys, almost all privately insured people understand the basic elements of their insurance plans but underestimate their coverage for mental health, substance abuse, and prescription drug benefits and overestimate their coverage for long-term care. People who are newly insured in physician networks or health maintenance organizations seem uncertain about what services their plan covers and restrictions on their choice of hospitals.