One Sentence SummaryWe demonstrate that continued presence of CXCR5 +/+ TFH cells throughout chronic viral infection is dispensable for maintenance of overall virus-specific antibody titers but is vital for the generation of virus-neutralizing antibodies and eventual control of the infection.
Highlights d Chronic infection reveals sustained clonal diversity of induced antibodies d Antibody repertoires attain a personalized signature during chronic infection d Chronic viral infection shows sustained GC response and PC differentiation d Chronic infection selects for higher-affinity antibodies than acute infection
Cytomegalovirus-based vaccine vectors offer interesting opportunities for T cell-based vaccination purposes as CMV infection induces large numbers of functional effector-like cells that accumulate in peripheral tissues, a process termed memory inflation. Maintenance of high numbers of peripheral CD8 T cells requires continuous replenishment of the inflationary T cell pool. Here, we show that the inflationary T cell population contains a small subset of cells expressing the transcription factor Tcf1. These Tcf1+ cells resemble central memory T cells and are proliferation competent. Upon sensing viral reactivation events, Tcf1+ cells feed into the pool of peripheral Tcf1− cells and depletion of Tcf1+ cells hampers memory inflation. TCR repertoires of Tcf1+ and Tcf1− populations largely overlap, with the Tcf1+ population showing higher clonal diversity. These data show that Tcf1+ cells are necessary for sustaining the inflationary T cell response, and upholding this subset is likely critical for the success of CMV-based vaccination approaches.
Members of the genus Burkholderia are versatile bacteria capable of colonizing highly diverse environmental niches. In this study, we investigated the global response of the opportunistic pathogen Burkholderia cenocepacia H111 to nitrogen limitation at the transcript and protein expression levels. In addition to a classical response to nitrogen starvation, including the activation of glutamine synthetase, PII proteins, and the two-component regulatory system NtrBC, B. cenocepacia H111 also upregulated polyhydroxybutyrate (PHB) accumulation and exopolysaccharide (EPS) production in response to nitrogen shortage. A search for consensus sequences in promoter regions of nitrogen-responsive genes identified a 54 consensus sequence. The mapping of the 54 regulon as well as the characterization of a 54 mutant suggests an important role of 54 not only in control of nitrogen metabolism but also in the virulence of this organism.
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