T cells translate individual, quantal activation into collective, analog cytokine responses via time-integrated feedbacks.

Variability within isogenic T cell populations yields heterogeneous 'local' signaling responses to shared antigenic stimuli, but responding clones may communicate 'global' antigen load through paracrine messengers, such as cytokines. Such coordination of individual cell responses within multicellular populations is critical for accurate collective reactions to shared environmental cues. However, cytokine production may saturate as a function of antigen input, or be dominated by the precursor frequency of antigen-specific T cells.

Distinct influences of peptide-MHC quality and quantity on in vivo T-cell responses.

The strength of T-cell receptor (TCR) stimulation and subsequent T-cell response depend on a combination of peptide-major histocompatibility complex (pMHC) density and potency. By comparing two different pMHC at doses yielding similar proliferation in vivo, we have highlighted unexpected differences in the qualitative and quantitative effects of TCR ligand. Measurements of cytokine sensitivity and two-photon imaging of T cell-dendritic cell (T-DC) interactions reveal discrimination between comparably weak stimuli resulting from either decreased pMHC potency or pMHC density.

Single-cell quantification of IL-2 response by effector and regulatory T cells reveals critical plasticity in immune response.

Understanding how the immune system decides between tolerance and activation by antigens requires addressing cytokine regulation as a highly dynamic process. We quantified the dynamics of interleukin-2 (IL-2) signaling in a population of T cells during an immune response by combining in silico modeling and single-cell measurements in vitro. We demonstrate that IL-2 receptor expression levels vary widely among T cells creating a large variability in the ability of the individual cells to consume, produce and participate in IL-2 signaling within the population.

Cardiac contraction affects respiratory airflow in the term newborn infant.

In studies in the newborn infant, it is often assumed that there are similarities in airflow in successive breaths, and, therefore, it is only necessary to measure parameters in a small number of breaths. However, other studies have shown considerable variability in breathing patterns in successive breaths. It was, therefore, decided to examine the variability in the patterns of airflow.

Optimization of inspiratory work in periodic breathing in infants.

In periodic breathing, there are repeated cycles of bursts of breaths separated by pauses several seconds long. We consider the mechanics of periodic breathing in human infants using calibrated traces of tidal volume and esophageal pressure recorded during the first few days after delivery. Each cycle of periodic breathing was analyzed in terms of the inspiratory time and beginning and end inspiratory volumes for each breath, the number of breaths in the cycle, and the total observed inspiratory work.