Pluto Bioinformatics

GSE106554: Systemic inflammation drives rapid conversion of conventional CD4+ T cells to Treg in vivo

Bulk RNA sequencing

The immune system faces a task that approximates cognition in its complexity as it processes a multitude of intrinsic and extrinsic signals and integrates these into responses of the appropriate class, specificity, magnitude, and duration for a given threat, with the hosts life often depending on the outcome. CD4+T lymphocytes occupy a unique role in the generation and regulation of immunity within this context and influence multiple innate and adaptive cell types. With respect to CD8+cytotoxic T lymphocytes (CTL), CD4+ T cells function early in the response as helpers (TH) to increase its magnitude and functionality, and later as regulatory cells (Treg) to restore homeostasis and avoid immune pathology. Using aListeriamonocytogenes (Lm) infection model, we probed whether the conditions of initial pathogen encounter could influence the generation of THversus Treg. At low dose infection, CD4+T cells help CTLs via CD40-CD40L signaling, while high dose infection induces rapid polyclonal conversion to functional FoxP3+CD25+Tregwithin 24 hours. These findings resolve long-standing questions regarding the requirement for TH and reveal a remarkable degree of plasticity in the function of CD4+T cells, which can be quickly converted to Tregin vivoin response to acute inflammation. SOURCE: Joseph,Samuel,Dolina La Jolla Institute for Allergy and Immunology