Evidence for a step-wise program of T cell development within the human tonsil

Professional Biological Sciences: 2nd Place (The Ohio State University Edward F. Hayes Graduate Research Forum)Human T cell development within the thymus is a well-characterized event, and it is known that a functional thymus is required for normal T cell generation to take place. Individuals with poor thymic function, from either congenital abnormality or post-natal injury, have a difficult time mounting a proper immune response and suffer from debilitating immune deficiency. Thus, it would be highly beneficial to identify an extrathymic human tissue that can support T cell differentiation so that we may eventually augment T cell production in these individuals. However, to date, no definitive site of extrathymic T cell development has been established. In this study, we used flow cytometry to identify five populations of putative extrathymic T cell precursors within the human pediatric tonsil. These populations range from an early CD34+CD38dimLin- subset all the way to a CD1a+CD4+CD8+CD3+/- double positive pre-T cell. Each subset identified phenotypically resembles the same population found in the human thymus, suggesting that there is considerable similarity between the cells in each of these two tissues. Furthermore, each putative extrathymic T cell developmental intermediate found within the tonsil retains the ability to develop into a mature CD3+ T cell. Thus, our data suggest that the human tonsil contains a full spectrum of T cell developmental intermediates that are remarkably similar to those found in the human thymus, and that the tonsil may be an extrathymic site which supports complete T cell differentiation.A five-year embargo was granted for this item

Models of classroom assessment for course-based research experiences

Course-based research pedagogy involves positioning students as contributors to authentic research projects as part of an engaging educational experience that promotes their learning and persistence in science. To develop a model for assessing and grading students engaged in this type of learning experience, the assessment aims and practices of a community of experienced course-based research instructors were collected and analyzed. This approach defines four aims of course-based research assessment—(1) Assessing Laboratory Work and Scientific Thinking; (2) Evaluating Mastery of Concepts, Quantitative Thinking and Skills; (3) Appraising Forms of Scientific Communication; and (4) Metacognition of Learning—along with a set of practices for each aim. These aims and practices of assessment were then integrated with previously developed models of course-based research instruction to reveal an assessment program in which instructors provide extensive feedback to support productive student engagement in research while grading those aspects of research that are necessary for the student to succeed. Assessment conducted in this way delicately balances the need to facilitate students’ ongoing research with the requirement of a final grade without undercutting the important aims of a CRE education

The Transcription Factor AHR Prevents the Differentiation of a Stage 3 Innate Lymphoid Cell Subset to Natural Killer Cells

Accumulating evidence indicates that human natural killer (NK) cells develop in secondary lymphoid tissue (SLT) through a so-called “stage 3” developmental intermediate minimally characterized by a CD34−CD117+CD94− immunophenotype that lacks mature NK cell function. This stage 3 population is heterogeneous, potentially composed of functionally distinct innate lymphoid cell (ILC) types that include interleukin-1 receptor (IL-1R1)-positive, IL-22-producing ILC3s. Whether human ILC3s are developmentally related to NK cells is a subject of ongoing investigation. Here, we show that antagonism of the aryl hydrocarbon receptor (AHR) or silencing of AHR gene expression promotes the differentiation of tonsillar IL-22-producing IL-1R1hi human ILC3s to CD56brightCD94+ interferon (IFN)-γ-producing cytolytic mature NK cells expressing eomesodermin (EOMES) and T-Box Protein 21 (TBX21 or TBET). Hence, we demonstrate the lineage plasticity of human ILCs by identifying AHR as a transcription factor that prevents IL-1R1hi ILC3s from differentiating into NK cells

CD94 surface density identifies a functional intermediary between the CD56bright and CD56dim human NK-cell subsets

Human CD56bright natural killer (NK) cells possess little or no killer immunoglobulin-like receptors (KIRs), high interferon-γ (IFN-γ) production, but little cytotoxicity. CD56dim NK cells have high KIR expression, produce little IFN-γ, yet display high cytotoxicity. We hypothesized that, if human NK maturation progresses from a CD56bright to a CD56dim phenotype, an intermediary NK cell must exist, which demonstrates more functional overlap than these 2 subsets, and we used CD94 expression to test our hypothesis. CD94highCD56dim NK cells express CD62L, CD2, and KIR at levels between CD56bright and CD94lowCD56dim NK cells. CD94highCD56dim NK cells produce less monokine-induced IFN-γ than CD56bright NK cells but much more than CD94lowCD56dim NK cells because of differential interleukin-12–mediated STAT4 phosphorylation. CD94highCD56dim NK cells possess a higher level of granzyme B and perforin expression and CD94-mediated redirected killing than CD56bright NK cells but lower than CD94lowCD56dim NK cells. Collectively, our data suggest that the density of CD94 surface expression on CD56dim NK cells identifies a functional and likely developmental intermediary between CD56bright and CD94lowCD56dim NK cells. This supports the notion that, in vivo, human CD56bright NK cells progress through a continuum of differentiation that ends with a CD94lowCD56dim phenotype