Keystone Symposia On Molecular and Cellular Biology

Scientific conferences play an important role in advancing research, scholarship, and the careers of emerging scientists. The COVID-19 pandemic offered meeting organizers and researchers alike an opportunity to reimagine what scientific conferences could look like. Virtual conferences can increase inclusivity and accessibility while decreasing costs and carbon emissions. However, it is generally perceived that the digital world fails to adequately recapitulate many of the benefits of in-person face-to-face interactions; these include socializing, and collaborative environments that can forge new research directions and provide critical career development opportunities. On November 15 and 16, 2022, researchers, representatives from diverse scientific conference organizations, leaders in virtual platform technologies, and innovators in conference design gathered online for the Open Access Keystone eSymposium "Reimagining Scientific Conferences." The meeting focused on how conference organizers can leverage lessons from the pandemic and emerging virtual platforms to engage new audiences, rethink strategies for scientific exchange, and decrease the carbon footprint of in-person events.

Immunologists appreciate the need for creative approaches to tackle complex scientific questions, which can involve not only the use of novel technologies but also the experience of scientists from diverse backgrounds. Here, we highlight measures to prime for the inclusion of women and underrepresented individuals in science to boost immunology research.

Regulatory CD4(+)Foxp3(+) T cells (Tregs) are key regulators of inflammatory responses and control the magnitude of cellular immune responses to viral infections. However, little is known about how Tregs contribute to immune regulation during memory responses to previously encountered pathogens. In this study, we used MHC class II tetramers specific for the 311-325 peptide from influenza nucleoprotein (NP311-325/IA(b)) to track the Ag-specific Treg response to primary and secondary influenza virus infections. During secondary infections, Ag-specific memory Tregs showed accelerated accumulation in the lung-draining lymph node and lung parenchyma relative to a primary infection. Memory Tregs effectively controlled the in vitro proliferation of memory CD8(+) cells in an Ag-specific fashion that was MHC class II dependent. When memory Tregs were depleted before secondary infection, the magnitude of the Ag-specific memory CD8(+) T cell response was increased, as was pulmonary inflammation and airway cytokine/chemokine expression. Replacement of memory Tregs with naive Tregs failed to restore the regulation of the memory CD8 T cell response during secondary infection. Together, these data demonstrate the existence of a previously undescribed population of Ag-specific memory Tregs that shape the cellular immune response to secondary influenza virus challenges and offer an additional parameter to consider when determining the efficacy of vaccinations.

Fully functional T cells are necessary for the maintenance of protective immunity during chronic infections. However, activated T cells often undergo apoptosis or exhaustion upon chronic stimulation mediated by Ag or inflammation. T cell attrition can be compensated for by the production of thymus-derived T cells, although the new naive T cells must undergo T cell priming and differentiation under conditions different from those encountered during acute infection. We used a murine model of Mycobacterium tuberculosis infection to address how the activation and differentiation of new thymic emigrants is affected by chronic inflammation, as well as whether the newly developed effector T cells help to maintain peripheral T cell responses. Although new thymic emigrants contributed to the peripheral T cell response early during acute M. tuberculosis infection, the relative contribution of new effector T cells to the peripheral CD4 and CD8 T cell pools declined during chronic infection. The decline in new T cell recruitment was a consequence of quantitative and/or qualitative changes in Ag presentation, because during chronic infection both the priming and expansion of naive T cells were inefficient. Thus, although thymic tolerance is not a major factor that limits protective T cell responses, the chronic environment does not efficiently support naive T cell priming and accumulation during M. tuberculosis infection. These studies support our previous findings that long-term protective T cell responses can be maintained indefinitely in the periphery, but also suggest that the perturbation of homeostasis during chronic inflammatory responses may elicit immune pathology mediated by new T cells.

Abstract Vitamin A deficiency (VAD) has profound effects on immune responses in the gut, but its influence on other mucosal sites is less well understood. Sendai virus (SeV) is a candidate human parainfluenza virus type I (hPIV-1) vaccine, and a candidate vaccine vector for other respiratory viruses. A single I.N. dose of SeV elicits a protective immune response against hPIV-1 within days after vaccination. To define the effect of VAD on responses toward SeV, we monitored antibody forming cells (AFC) and immunodominant CD8+ T cells in mice. VAD inhibited SeV-specific IgA producing AFCs in the upper respiratory tract (URT) and biased the AFC response in favor of IgG-producing cells in the lower respiratory tract (LRT). In contrast, there was a dramatic reduction of CD8+ T cell frequencies in the LRT airways of VAD animals. Responding CD8+ T cells exhibited unusually high CD103 expression. In both VAD and control mice, e-cadherin (the ligand for αE(CD103)β7) was well expressed in URT tissues, but was expressed only weakly in the LRT. Results support a working hypothesis that the high CD103 expression among responding T cells in VAD mice may enhance T cell entrapment by e-cadherin and inhibit cell egress into the LRT airway. Our results highlight the concept that VAD does not exclusively affect immune responses in the gut, but has dramatic influences on immune cell function and residence in the respiratory tract.